Table of Contents Author Guidelines Submit a Manuscript
Scientifica
Volume 2012, Article ID 857516, 26 pages
http://dx.doi.org/10.6064/2012/857516
Review Article

Endoplasmic Reticulum Stress: Its Role in Disease and Novel Prospects for Therapy

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR-405, Los Angeles, CA 90033, USA

Received 9 October 2012; Accepted 12 November 2012

Academic Editors: M. S. Abu-Asab, R. Matthiesen, and I. Pérez De Castro

Copyright © 2012 Axel H. Schönthal. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. Alberts, A. Johnson, J. Lewis et al., Molecular Biology of the Cell, Garland Science, New York, NY, USA, 5th edition, 2008.
  2. J. D. Malhotra and R. J. Kaufman, “The endoplasmic reticulum and the unfolded protein response,” Seminars in Cell and Developmental Biology, vol. 18, no. 6, pp. 716–731, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. D. Ron and P. Walter, “Signal integration in the endoplasmic reticulum unfolded protein response,” Nature Reviews Molecular Cell Biology, vol. 8, no. 7, pp. 519–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Bernales, K. L. McDonald, and P. Walter, “Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response,” PLoS Biology, vol. 4, no. 12, article e423, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. W. X. Ding, H. M. Ni, W. Gao et al., “Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival,” Journal of Biological Chemistry, vol. 282, no. 7, pp. 4702–4710, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Ogata, S. I. Hino, A. Saito et al., “Autophagy is activated for cell survival after endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 26, no. 24, pp. 9220–9231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. T. Yorimitsu, U. Nair, Z. Yang, and D. J. Klionsky, “Endoplasmic reticulum stress triggers autophagy,” Journal of Biological Chemistry, vol. 281, no. 40, pp. 30299–30304, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. J. J. Yin, Y. B. Li, Y. Wang et al., “The role of autophagy in endoplasmic reticulum stressinduced pancreatic beta cell death,” Autophagy, vol. 8, pp. 158–164, 2012. View at Google Scholar
  9. S. M. Schleicher, L. Moretti, V. Varki, and B. Lu, “Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: implications for future therapeutic approaches,” Drug Resistance Updates, vol. 13, no. 3, pp. 79–86, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. E. J. White, V. Martin, J. L. Liu et al., “Autophagy regulation in cancer development and therapy,” American Journal of Cancer Research, vol. 1, pp. 362–372, 2011. View at Google Scholar
  11. S. Zhou, L. Zhao, M. Kuang et al., “Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?” Cancer Letters, vol. 323, pp. 115–127, 2012. View at Google Scholar
  12. D. C. Rubinsztein, P. Codogno, and B. Levine, “Autophagy modulation as a potential therapeutic target for diverse diseases,” Nature Reviews Drug Discovery, vol. 11, pp. 709–730, 2012. View at Google Scholar
  13. T. Hartley, M. Siva, E. Lai, T. Teodoro, L. Zhang, and A. Volchuk, “Endoplasmic reticulum stress response in an INS-1 pancreatic β-cell line with inducible expression of a folding-deficient proinsulin,” BMC Cell Biology, vol. 11, article 59, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. G. Raposo, H. M. van Santen, R. Leijendekker, H. J. Geuze, and H. L. Ploegh, “Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment,” Journal of Cell Biology, vol. 131, no. 6 I, pp. 1403–1419, 1995. View at Publisher · View at Google Scholar · View at Scopus
  15. A. A. Welihinda, W. Tirasophon, and R. J. Kaufman, “The cellular response to protein misfolding in the endoplasmic reticulum,” Gene Expression, vol. 7, no. 4–6, pp. 293–300, 1999. View at Google Scholar · View at Scopus
  16. C. Zuber, J. Y. Fan, B. Guhl, and J. Roth, “Misfolded proinsulin accumulates in expanded pre-Golgi intermediates and endoplasmic reticulum subdomains in pancreatic beta cells of Akita mice,” The FASEB Journal, vol. 18, no. 7, pp. 917–919, 2004. View at Google Scholar · View at Scopus
  17. F. Despa, “Dilation of the endoplasmic reticulum in beta cells due to molecular overcrowding? Kinetic simulations of extension limits and consequences on proinsulin synthesis,” Biophysical Chemistry, vol. 140, no. 1–3, pp. 115–121, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. I. G. Haas and M. Wabl, “Immunoglobulin heavy chain binding protein,” Nature, vol. 306, no. 5941, pp. 387–389, 1983. View at Google Scholar · View at Scopus
  19. S. Munro and H. R. B. Pelham, “An hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein,” Cell, vol. 46, no. 2, pp. 291–300, 1986. View at Google Scholar · View at Scopus
  20. M. Csala, E. Kereszturi, J. Mandl, and G. Banhegyi, “The endoplasmic reticulum as the extracellular space inside the cell: role in protein folding and glycosylation,” Antioxidants and Redox Signaling, vol. 16, pp. 1100–1108, 2012. View at Google Scholar
  21. J. Roth, C. Zuber, S. Park et al., “Protein N-glycosylation, protein folding, and protein quality control,” Molecules and Cells, vol. 30, no. 6, pp. 497–506, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Hagiwara and K. Nagata, “Redox-dependent protein quality control in the endoplasmic reticulum: folding to degradation,” Antioxidants and Redox Signaling, vol. 16, pp. 1119–1128, 2012. View at Google Scholar
  23. Y. Ma and L. M. Hendershot, “ER chaperone functions during normal and stress conditions,” Journal of Chemical Neuroanatomy, vol. 28, no. 1-2, pp. 51–65, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. J. Krebs, J. Groenendyk, and M. Michalak, “Ca2+-signaling, alternative splicing and endoplasmic reticulum stress responses,” Neurochemical Research, vol. 36, no. 7, pp. 1198–1211, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. A. H. Schönthal, “Endoplasmic reticulum stress and autophagy as targets for cancer therapy,” Cancer Letters, vol. 275, no. 2, pp. 163–169, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Hideshima, J. E. Bradner, J. Wong et al., “Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 24, pp. 8567–8572, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Kawaguchi, J. J. Kovacs, A. McLaurin, J. M. Vance, A. Ito, and T. P. Yao, “The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress,” Cell, vol. 115, no. 6, pp. 727–738, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. A. von dem Bussche, R. Machida, K. Li et al., “Hepatitis C virus NS2 protein triggers endoplasmic reticulum stress and suppresses its own viral replication,” Journal of Hepatology, vol. 53, pp. 797–804, 2010. View at Google Scholar
  29. B. He, “Viruses, endoplasmic reticulum stress, and interferon responses,” Cell Death and Differentiation, vol. 13, no. 3, pp. 393–403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. C. R. Roy, S. P. Salcedo, and J. P. E. Gorvel, “Pathogen-endoplasmic-reticulum interactions: in through the out door,” Nature Reviews Immunology, vol. 6, no. 2, pp. 136–147, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. S. H. Back and R. J. Kaufman, “Endoplasmic reticulum stress and type 2 diabetes,” Annual Review of Biochemistry, vol. 81, pp. 767–793, 2012. View at Google Scholar
  32. L. Dara, C. Ji, and N. Kaplowitz, “The contribution of endoplasmic reticulum stress to liver diseases,” Hepatology, vol. 53, no. 5, pp. 1752–1763, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Fu, S. M. Watkins, and G. S. Hotamisligil, “The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling,” Cell Metabolism, vol. 15, pp. 623–634, 2012. View at Google Scholar
  34. U. Özcan, Q. Cao, E. Yilmaz et al., “Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes,” Science, vol. 306, no. 5695, pp. 457–461, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. A. S. Lee, “The glucose-regulated proteins: stress induction and clinical applications,” Trends in Biochemical Sciences, vol. 26, no. 8, pp. 504–510, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. A. S. Lee, A. Delegeane, and D. Scharff, “Highly conserved glucose-regulated protein in hamster and chicken cells: preliminary characterization of its cDNA clone,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 8 I, pp. 4922–4925, 1981. View at Google Scholar · View at Scopus
  37. S. J. M. Healy, A. M. Gorman, P. Mousavi-Shafaei, S. Gupta, and A. Samali, “Targeting the endoplasmic reticulum-stress response as an anticancer strategy,” European Journal of Pharmacology, vol. 625, no. 1–3, pp. 234–246, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Luo and A. S. Lee, “The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies,” Oncogene. In press.
  39. L. H. Zhang and X. Zhang, “Roles of GRP78 in physiology and cancer,” Journal of Cellular Biochemistry, vol. 110, no. 6, pp. 1299–1305, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Ni, H. Zhou, S. Wey, P. Baumeister, and A. S. Lee, “Regulation of PERK signaling and leukemic cell survival by a novel cytosolic isoform of the UPR regulator GRP78/BiP,” PLoS ONE, vol. 4, no. 8, Article ID e6868, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. F. C. Sun, S. Wei, C. W. Li, Y. S. Chang, C. C. Chao, and Y. K. Lai, “Localization of GRP78 to mitochondria under the unfolded protein response,” Biochemical Journal, vol. 396, no. 1, pp. 31–39, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Matsumoto and P. C. Hanawalt, “Histone H3 and heat shock protein GRP78 are selectively cross-linked to DNA by photoactivated gilvocarcin V in human fibroblasts,” Cancer Research, vol. 60, no. 14, pp. 3921–3926, 2000. View at Google Scholar · View at Scopus
  43. M. A. Arap, J. Lahdenranta, P. J. Mintz et al., “Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands,” Cancer Cell, vol. 6, no. 3, pp. 275–284, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. U. K. Misra, R. Deedwania, and S. V. Pizzo, “Activation and cross-talk between Akt, NF-κB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78,” Journal of Biological Chemistry, vol. 281, no. 19, pp. 13694–13707, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Shani, W. H. Fischer, N. J. Justice, J. A. Kelber, W. Vale, and P. C. Gray, “GRP78 and cripto form a complex at the cell surface and collaborate to inhibit transforming growth factor β signaling and enhance cell growth,” Molecular and Cellular Biology, vol. 28, no. 2, pp. 666–677, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Zhang, R. Liu, M. Ni, P. Gill, and A. S. Lee, “Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP,” Journal of Biological Chemistry, vol. 285, no. 20, pp. 15065–15075, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Liu, S. C. J. Steiniger, Y. Kim, G. F. Kaufmann, B. Felding-Habermann, and K. D. Janda, “Mechanistic studies of a peptidic GRP78 ligand for cancer cell-specific drug delivery,” Molecular Pharmaceutics, vol. 4, no. 3, pp. 435–447, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Ni, Y. Zhang, and A. S. Lee, “Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting,” Biochemical Journal, vol. 434, no. 2, pp. 181–188, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. D. Ron and S. R. Hubbard, “How IRE1 reacts to ER stress,” Cell, vol. 132, no. 1, pp. 24–26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. D. R. Fels and C. Koumenis, “The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth,” Cancer Biology and Therapy, vol. 5, pp. 723–728, 2006. View at Google Scholar
  51. T. Sommer and E. Jarosch, “BiP binding keeps ATF6 at bay,” Developmental Cell, vol. 3, no. 1, pp. 1–2, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. V. M. Parmar and M. Schroder, “Sensing endoplasmic reticulum stress,” Advances in Experimental Medicine and Biology, vol. 738, pp. 153–168, 2012. View at Google Scholar
  53. C. Patil and P. Walter, “Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals,” Current Opinion in Cell Biology, vol. 13, no. 3, pp. 349–355, 2001. View at Google Scholar · View at Scopus
  54. K. Kohno, “Stress-sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals,” Journal of Biochemistry, vol. 147, no. 1, pp. 27–33, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. A. L. Shaffer, M. Shapiro-Shelef, N. N. Iwakoshi et al., “XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation,” Immunity, vol. 21, no. 1, pp. 81–93, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. N. N. Iwakoshi, A. H. Lee, P. Vallabhajosyula, K. L. Otipoby, K. Rajewsky, and L. H. Glimcher, “Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-I,” Nature Immunology, vol. 4, no. 4, pp. 321–329, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. I. Braakman and N. J. Bulleid, “Protein folding and modification in the mammalian endoplasmic reticulum,” Annual Review of Biochemistry, vol. 80, pp. 71–99, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Jäger, M. J. Bertrand, A. M. Gorman et al., “The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress,” Biology of the Cell, vol. 104, pp. 259–270, 2012. View at Google Scholar
  59. H. Nishitoh, A. Matsuzawa, K. Tobiume et al., “ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats,” Genes and Development, vol. 16, no. 11, pp. 1345–1355, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Urano, X. Wang, A. Bertolotti et al., “Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1,” Science, vol. 287, no. 5453, pp. 664–666, 2000. View at Publisher · View at Google Scholar · View at Scopus
  61. D. N. Dhanasekaran and E. P. Reddy, “JNK signaling in apoptosis,” Oncogene, vol. 27, no. 48, pp. 6245–6251, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. R. Kim, M. Emi, K. Tanabe, and S. Murakami, “Role of the unfolded protein response in cell death,” Apoptosis, vol. 11, no. 1, pp. 5–13, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. K. Haze, H. Yoshida, H. Yanagi, T. Yura, and K. Mori, “Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress,” Molecular Biology of the Cell, vol. 10, no. 11, pp. 3787–3799, 1999. View at Google Scholar · View at Scopus
  64. K. Yamamoto, T. Sato, T. Matsui et al., “Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1,” Developmental Cell, vol. 13, no. 3, pp. 365–376, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. Adachi, K. Yamamoto, T. Okada, H. Yoshida, A. Harada, and K. Mori, “ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum,” Cell Structure and Function, vol. 33, no. 1, pp. 75–89, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. H. Yoshida, T. Matsui, A. Yamamoto, T. Okada, and K. Mori, “XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor,” Cell, vol. 107, no. 7, pp. 881–891, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. D. Bailey and P. O'Hare, “Transmembrane bZIP transcription factors in ER stress signaling and the unfolded protein response,” Antioxidants and Redox Signaling, vol. 9, no. 12, pp. 2305–2321, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. H. P. Harding, Y. Zhang, A. Bertolotti, H. Zeng, and D. Ron, “Perk is essential for translational regulation and cell survival during the unfolded protein response,” Molecular Cell, vol. 5, no. 5, pp. 897–904, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Nishitoh, “CHOP is a multifunctional transcription factor in the ER stress response,” Journal of Biochemistry, vol. 151, pp. 217–219, 2012. View at Google Scholar
  70. S. B. Cullinan and J. A. Diehl, “PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress,” Journal of Biological Chemistry, vol. 279, no. 19, pp. 20108–20117, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. S. B. Cullinan and J. A. Diehl, “Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway,” International Journal of Biochemistry and Cell Biology, vol. 38, no. 3, pp. 317–332, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. S. B. Cullinan, D. Zhang, M. Hannink, E. Arvisais, R. J. Kaufman, and J. A. Diehl, “Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival,” Molecular and Cellular Biology, vol. 23, no. 20, pp. 7198–7209, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. B. D. Price and S. K. Calderwood, “Gadd45 and gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose- regulated proteins,” Cancer Research, vol. 52, no. 13, pp. 3814–3817, 1992. View at Google Scholar · View at Scopus
  74. A. J. Fornace Jr., D. W. Nebert, M. C. Hollander et al., “Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents,” Molecular and Cellular Biology, vol. 9, no. 10, pp. 4196–4203, 1989. View at Google Scholar · View at Scopus
  75. K. D. McCullough, J. L. Martindale, L. O. Klotz, T. Y. Aw, and N. J. Holbrook, “Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bc12 and perturbing the cellular redox state,” Molecular and Cellular Biology, vol. 21, no. 4, pp. 1249–1259, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Puthalakath, L. A. O'Reilly, P. Gunn et al., “ER stress triggers apoptosis by activating BH3-only protein Bim,” Cell, vol. 129, no. 7, pp. 1337–1349, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. H. Malhi and R. J. Kaufman, “Endoplasmic reticulum stress in liver disease,” Journal of Hepatology, vol. 54, no. 4, pp. 795–809, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. H. Yamaguchi and H. G. Wang, “CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells,” Journal of Biological Chemistry, vol. 279, no. 44, pp. 45495–45502, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Kojima, A. Takeuchi, M. Haneda et al., “The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice,” The FASEB Journal, vol. 17, no. 11, pp. 1573–1575, 2003. View at Google Scholar · View at Scopus
  80. I. Novoa, H. Zeng, H. P. Harding, and D. Ron, “Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α,” Journal of Cell Biology, vol. 153, no. 5, pp. 1011–1022, 2001. View at Google Scholar · View at Scopus
  81. D. T. Rutkowski, S. M. Arnold, C. N. Miller et al., “Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins,” PLoS Biology, vol. 4, no. 11, article e374, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Dong, M. Ni, J. Li et al., “Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development,” Cancer Research, vol. 68, no. 2, pp. 498–505, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. P. M. Fernandez, S. O. Tabbara, L. K. Jacobs et al., “Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions,” Breast Cancer Research and Treatment, vol. 59, no. 1, pp. 15–26, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. G. Gazit, J. Lu, and A. S. Lee, “De-regulation of GRP stress protein expression in human breast cancer cell lines,” Breast Cancer Research and Treatment, vol. 54, no. 2, pp. 135–146, 1999. View at Publisher · View at Google Scholar · View at Scopus
  85. E. Lee, P. Nichols, D. Spicer, S. Groshen, M. C. Yu, and A. S. Lee, “GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer,” Cancer Research, vol. 66, no. 16, pp. 7849–7853, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. J. Wang, Y. Yin, H. Hua et al., “Blockade of GRP78 sensitizes breast cancer cells to microtubules-interfering agents that induce the unfolded protein response,” Journal of Cellular and Molecular Medicine, vol. 13, no. 9 B, pp. 3888–3897, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. G. Verma and M. Datta, “The critical role of JNK in the ER-mitochondrial crosstalk during apoptotic cell death,” Journal of Cellular Physiology, vol. 227, pp. 1791–1795, 2012. View at Publisher · View at Google Scholar
  88. I. Kim, C. W. Shu, W. Xu et al., “Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1,” Journal of Biological Chemistry, vol. 284, no. 3, pp. 1593–1603, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Hetz and L. H. Glimcher, “Fine-tuning of the unfolded protein response: assembling the IRE1α interactome,” Molecular Cell, vol. 35, no. 5, pp. 551–561, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. G. C. Shore, F. R. Papa, and S. A. Oakes, “Signaling cell death from the endoplasmic reticulum stress response,” Current Opinion in Cell Biology, vol. 23, no. 2, pp. 143–149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Oyadomari and M. Mori, “Roles of CHOP/GADD153 in endoplasmic reticulum stress,” Cell Death and Differentiation, vol. 11, no. 4, pp. 381–389, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Hitomi, T. Katayama, Y. Eguchi et al., “Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Aβ-induced cell death,” Journal of Cell Biology, vol. 165, no. 3, pp. 347–356, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Boyce and J. Yuan, “Cellular response to endoplasmic reticulum stress: a matter of life or death,” Cell Death and Differentiation, vol. 13, no. 3, pp. 363–373, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. T. Suzuki, J. Lu, M. Zahed, K. Kita, and N. Suzuki, “Reduction of GRP78 expression with siRNA activates unfolded protein response leading to apoptosis in HeLa cells,” Archives of Biochemistry and Biophysics, vol. 468, no. 1, pp. 1–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. A. S. Lee, “GRP78 induction in cancer: therapeutic and prognostic implications,” Cancer Research, vol. 67, no. 8, pp. 3496–3499, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. A. H. Schönthal, T. C. Chen, F. M. Hofman et al., “Preclinical development of novel antitumor drugs targeting the endoplasmic reticulum stress response,” Current Pharmaceutical Design, vol. 17, pp. 2428–2438, 2011. View at Google Scholar
  97. A. Kardosh, E. B. Golden, P. Pyrko et al., “Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib,” Cancer Research, vol. 68, no. 3, pp. 843–851, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. M. Cnop, F. Foufelle, and L. A. Velloso, “Endoplasmic reticulum stress, obesity and diabetes,” Trends in Molecular Medicine, vol. 18, pp. 59–68, 2012. View at Google Scholar
  99. D. Scheuner and R. J. Kaufman, “The unfolded protein response: a pathway that links insulin demand with β-cell failure and diabetes,” Endocrine Reviews, vol. 29, no. 3, pp. 317–333, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Ozcan and I. Tabas, “Role of endoplasmic reticulum stress in metabolic disease and other disorders,” Annual Review of Medicine, vol. 63, pp. 317–328, 2012. View at Google Scholar
  101. D. L. Eizirik, A. K. Cardozo, and M. Cnop, “The role for endoplasmic reticulum stress in diabetes mellitus,” Endocrine Reviews, vol. 29, no. 1, pp. 42–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. J. E. Shaw, R. A. Sicree, and P. Z. Zimmet, “Global estimates of the prevalence of diabetes for 2010 and 2030,” Diabetes Research and Clinical Practice, vol. 87, no. 1, pp. 4–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. C. L. Gentile, M. Frye, and M. J. Pagliassotti, “Endoplasmic reticulum stress and the unfolded protein response in nonalcoholic fatty liver disease,” Antioxidants and Redox Signaling, vol. 15, no. 2, pp. 505–521, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Cnop, J. Vidal, R. L. Hull et al., “Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes,” Diabetes Care, vol. 30, no. 3, pp. 677–682, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Cnop, N. Welsh, J. C. Jonas, A. Jörns, S. Lenzen, and D. L. Eizirik, “Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities,” Diabetes, vol. 54, supplement 2, pp. S97–S107, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Festa, K. Williams, R. D'Agostino Jr., L. E. Wagenknecht, and S. M. Haffner, “The natural course of β-cell function in nondiabetic and diabetic individuals: the insulin resistance atherosclerosis study,” Diabetes, vol. 55, no. 4, pp. 1114–1120, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Weyer, C. Bogardus, D. M. Mott, and R. E. Pratley, “The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus,” Journal of Clinical Investigation, vol. 104, no. 6, pp. 787–794, 1999. View at Google Scholar · View at Scopus
  108. H. Sakuraba, H. Mizukami, N. Yagihashi, R. Wada, C. Hanyu, and S. Yagihashi, “Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients,” Diabetologia, vol. 45, no. 1, pp. 85–96, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. A. E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R. A. Rizza, and P. C. Butler, “β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes,” Diabetes, vol. 52, no. 1, pp. 102–110, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. K. H. Yoon, S. H. Ko, J. H. Cho et al., “Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, pp. 2300–2308, 2003. View at Google Scholar
  111. M. Prentki and C. J. Nolan, “Islet β cell failure in type 2 diabetes,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1802–1812, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. C. J. Huang, C. Y. Lin, L. Haataja et al., “High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress-mediated β-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes,” Diabetes, vol. 56, no. 8, pp. 2016–2027, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. S. Costes, C. J. Huang, T. Gurlo et al., “β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency,” Diabetes, vol. 60, no. 1, pp. 227–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Cnop, L. Ladriere, P. Hekerman et al., “Selective inhibition of eukaryotic translation initiation factor 2α dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic β-cell dysfunction and apoptosis,” Journal of Biological Chemistry, vol. 282, no. 6, pp. 3989–3997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. E. Karaskov, C. Scott, L. Zhang, T. Teodoro, M. Ravazzola, and A. Volchuk, “Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic β-cell apoptosis,” Endocrinology, vol. 147, no. 7, pp. 3398–3407, 2006. View at Publisher · View at Google Scholar · View at Scopus
  116. I. Kharroubi, L. Ladrière, A. K. Cardozo, Z. Dogusan, M. Cnop, and D. L. Eizirik, “Free fatty acids and cytokines induce pancreatic β-cell apoptosis by different mechanisms: role of nuclear factor-κB and endoplasmic reticulum stress,” Endocrinology, vol. 145, no. 11, pp. 5087–5096, 2004. View at Publisher · View at Google Scholar · View at Scopus
  117. K. Komiya, T. Uchida, T. Ueno et al., “Free fatty acids stimulate autophagy in pancreatic β-cells via JNK pathway,” Biochemical and Biophysical Research Communications, vol. 401, no. 4, pp. 561–567, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. T. F. Kuo, H. Tatsukawa, T. Matsuura et al., “Free fatty acids induce transglutaminase 2-dependent apoptosis in hepatocytes via ER stress-stimulated PERK pathways,” Journal of Cellular Physiology, vol. 227, pp. 1130–1137, 2012. View at Google Scholar
  119. D. R. Laybutt, A. M. Preston, M. C. Åkerfeldt et al., “Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes,” Diabetologia, vol. 50, no. 4, pp. 752–763, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. H. Elouil, M. Bensellam, Y. Guiot et al., “Acute nutrient regulation of the unfolded protein response and integrated stress response in cultured rat pancreatic islets,” Diabetologia, vol. 50, no. 7, pp. 1442–1452, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. Z. Q. Hou, H. L. Li, L. Gao, L. Pan, J. J. Zhao, and G. W. Li, “Involvement of chronic stresses in rat islet and INS-1 cell glucotoxicity induced by intermittent high glucose,” Molecular and Cellular Endocrinology, vol. 291, no. 1-2, pp. 71–78, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. V. Aguirre, E. D. Werner, J. Giraud, Y. H. Lee, S. E. Shoelson, and M. F. White, “Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action,” Journal of Biological Chemistry, vol. 277, no. 2, pp. 1531–1537, 2002. View at Publisher · View at Google Scholar · View at Scopus
  123. H. P. Harding, H. Zeng, Y. Zhang et al., “Diabetes mellitus and exocrine pancreatic dysfunction in Perk-/- mice reveals a role for translational control in secretory cell survival,” Molecular Cell, vol. 7, no. 6, pp. 1153–1163, 2001. View at Publisher · View at Google Scholar · View at Scopus
  124. K. L. Lipson, S. G. Fonseca, S. Ishigaki et al., “Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1,” Cell Metabolism, vol. 4, no. 3, pp. 245–254, 2006. View at Publisher · View at Google Scholar · View at Scopus
  125. D. Scheuner, D. V. Mierde, B. Song et al., “Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis,” Nature Medicine, vol. 11, no. 7, pp. 757–764, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. M. Maris, L. Overbergh, C. Gysemans et al., “Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance,” Diabetologia, vol. 55, pp. 1167–1178, 2012. View at Google Scholar
  127. B. Song, D. Scheuner, D. Ron, S. Pennathur, and R. J. Kaufman, “Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes,” Journal of Clinical Investigation, vol. 118, no. 10, pp. 3378–3389, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. W. M. McKimpson, J. Weinberger, L. Czerski et al., “The apoptosis inhibitor ARC alleviates the ER stress response to promote beta-cell survival,” Diabetes. In press.
  129. U. Özcan, E. Yilmaz, L. Özcan et al., “Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes,” Science, vol. 313, no. 5790, pp. 1137–1140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  130. J. Zhou, S. Zhou, J. Tang et al., “Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats,” European Journal of Pharmacology, vol. 606, no. 1–3, pp. 262–268, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. W. Jia, W. Gaoz, and L. Tang, “Antidiabetic herbal drugs officially approved in China,” Phytotherapy Research, vol. 17, no. 10, pp. 1127–1134, 2003. View at Publisher · View at Google Scholar · View at Scopus
  132. W. Xie, Y. Zhao, and Y. Zhang, “Traditional chinese medicines in treatment of patients with type 2 diabetes mellitus,” Evidence-Based Complementary and Alternative Medicine, vol. 2011, Article ID 726723, 13 pages, 2011. View at Publisher · View at Google Scholar
  133. J. Yin, H. Zhang, and J. Ye, “Traditional Chinese medicine in treatment of metabolic syndrome,” Endocrine, Metabolic and Immune Disorders, vol. 8, no. 2, pp. 99–111, 2008. View at Publisher · View at Google Scholar · View at Scopus
  134. X. L. Tong, L. Dong, L. Chen, and Z. Zhen, “Treatment of diabetes using traditional chinese medicine: past, present and future,” The American Journal of Chinese Medicine, vol. 40, pp. 877–886, 2012. View at Google Scholar
  135. L. Ozcan, A. S. Ergin, A. Lu et al., “Endoplasmic reticulum stress plays a central role in development of leptin resistance,” Cell Metabolism, vol. 9, no. 1, pp. 35–51, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. J. C. Won, P. G. Jang, C. Namkoong et al., “Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin,” Obesity, vol. 17, no. 10, pp. 1861–1865, 2009. View at Publisher · View at Google Scholar · View at Scopus
  137. T. Hosoi, T. Miyahara, T. Kayano et al., “Fluvoxamine attenuated endoplasmic reticulum stress-induced leptin resistance,” Frontiers in Endocrinology, vol. 3, article 12, 2012. View at Google Scholar
  138. R. Coppari and C. Bjorbaek, “Leptin revisited: its mechanism of action and potential for treating diabetes,” Nature Reviews Drug Discovery, vol. 11, pp. 692–708, 2012. View at Google Scholar
  139. A. C. Konner and J. C. Bruning, “Selective insulin and leptin resistance in metabolic disorders,” Cell Metabolism, vol. 16, pp. 144–152, 2012. View at Google Scholar
  140. T. Hosoi, M. Sasaki, T. Miyahara et al., “Endoplasmic reticulum stress induces leptin resistance,” Molecular Pharmacology, vol. 74, no. 6, pp. 1610–1619, 2008. View at Publisher · View at Google Scholar · View at Scopus
  141. G. Marwarha, B. Dasari, and O. Ghribi, “Endoplasmic reticulum stress-induced CHOP activation mediates the down-regulation of leptin in human neuroblastoma SH-SY5Y cells treated with the oxysterol 27-hydroxycholesterol,” Cell Signaling, vol. 24, pp. 484–492, 2012. View at Google Scholar
  142. G. Boden, X. Duan, C. Homko et al., “Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals,” Diabetes, vol. 57, no. 9, pp. 2438–2444, 2008. View at Publisher · View at Google Scholar · View at Scopus
  143. N. K. Sharma, S. K. Das, A. K. Mondal et al., “Endoplasmic reticulum stress markers are associated with obesity in nondiabetic subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 11, pp. 4532–4541, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. M. F. Gregor, L. Yang, E. Fabbrini et al., “Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss,” Diabetes, vol. 58, no. 3, pp. 693–700, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. M. Kars, L. Yang, M. F. Gregor et al., “Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women,” Diabetes, vol. 59, no. 8, pp. 1899–1905, 2010. View at Publisher · View at Google Scholar · View at Scopus
  146. C. Xiao, A. Giacca, and G. F. Lewis, “Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and β-cell dysfunction in humans,” Diabetes, vol. 60, no. 3, pp. 918–924, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. H. R. Christofk, M. G. vander Heiden, M. H. Harris et al., “The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth,” Nature, vol. 452, no. 7184, pp. 230–233, 2008. View at Publisher · View at Google Scholar · View at Scopus
  148. P. P. Hsu and D. M. Sabatini, “Cancer cell metabolism: warburg and beyond,” Cell, vol. 134, no. 5, pp. 703–707, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. M. J. Prindle, E. J. Fox, and L. A. Loeb, “The mutator phenotype in cancer: molecular mechanisms and targeting strategies,” Current Drug Targets, vol. 11, no. 10, pp. 1296–1303, 2010. View at Google Scholar · View at Scopus
  150. R. J. Shaw, “Glucose metabolism and cancer,” Current Opinion in Cell Biology, vol. 18, pp. 598–608, 2006. View at Google Scholar
  151. P. Pyrko, A. H. Schöntha, F. M. Hofman, T. C. Chen, and A. S. Lee, “The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas,” Cancer Research, vol. 67, no. 20, pp. 9809–9816, 2007. View at Publisher · View at Google Scholar · View at Scopus
  152. J. J. Virrey, D. Dong, C. Stiles et al., “Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated endothelial cells,” Molecular Cancer Research, vol. 6, no. 8, pp. 1268–1275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  153. D. Dong, B. Ko, P. Baumeister et al., “Vascular targeting and antiangiogenesis agents induce drug resistance effector GRP78 within the tumor microenvironment,” Cancer Research, vol. 65, no. 13, pp. 5785–5791, 2005. View at Publisher · View at Google Scholar · View at Scopus
  154. Y. Fu and A. S. Lee, “Glucose regulated proteins in cancer progression, drug resistance and immunotherapy,” Cancer Biology and Therapy, vol. 5, no. 7, pp. 741–744, 2006. View at Google Scholar · View at Scopus
  155. J. Li and A. S. Lee, “Stress induction of GRP78/BiP and its role in cancer,” Current Molecular Medicine, vol. 6, no. 1, pp. 45–54, 2006. View at Publisher · View at Google Scholar · View at Scopus
  156. G. de Ridder, R. Ray, U. K. Misra, and S. V. Pizzo, “Modulation of the unfolded protein response by GRP78 in prostate cancer,” Methods in Enzymology, vol. 489, pp. 245–257, 2011. View at Publisher · View at Google Scholar · View at Scopus
  157. J. Li, M. Ni, B. Lee, E. Barron, D. R. Hinton, and A. S. Lee, “The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells,” Cell Death and Differentiation, vol. 15, no. 9, pp. 1460–1471, 2008. View at Publisher · View at Google Scholar · View at Scopus
  158. B. H. Y. Yeung, B. W. Y. Kwan, Q. Y. He, A. S. Lee, J. Liu, and A. S. T. Wong, “Glucose-regulated protein 78 as a novel effector of BRCA1 for inhibiting stress-induced apoptosis,” Oncogene, vol. 27, no. 53, pp. 6782–6789, 2008. View at Publisher · View at Google Scholar · View at Scopus
  159. T. Beddoe, A. W. Paton, J. Le Nours, J. Rossjohn, and J. C. Paton, “Structure, biological functions and applications of the AB5 toxins,” Trends in Biochemical Sciences, vol. 35, no. 7, pp. 411–418, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. A. W. Paton, T. Beddoe, C. M. Thorpe et al., “AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP,” Nature, vol. 443, no. 7111, pp. 548–552, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. J. M. Backer, A. V. Krivoshein, C. V. Hamby et al., “Chaperone-targeting cytotoxin and endoplasmic reticulum stress-inducing drug synergize to kill cancer cells,” Neoplasia, vol. 11, no. 11, pp. 1165–1173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  162. S. Nakajima, N. Hiramatsu, K. Hayakawa et al., “Selective abrogation of BiP/GRP78 blunts activation of NF-κB through the ATF6 branch of the UPR: involvement of C/EBPβ and mTOR-dependent dephosphorylation of Akt,” Molecular and Cellular Biology, vol. 31, no. 8, pp. 1710–1718, 2011. View at Publisher · View at Google Scholar · View at Scopus
  163. T. Tian, Y. Zhao, S. Nakajima et al., “Cytoprotective roles of ERK and Akt in endoplasmic reticulum stress triggered by subtilase cytotoxin,” Biochemical and Biophysical Research Communications, vol. 410, no. 4, pp. 852–858, 2011. View at Publisher · View at Google Scholar · View at Scopus
  164. H. Yamazaki, N. Hiramatsu, K. Hayakawa et al., “Activation of the Akt-NF-κB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response,” Journal of Immunology, vol. 183, no. 2, pp. 1480–1487, 2009. View at Publisher · View at Google Scholar · View at Scopus
  165. Y. Zhao, T. Tian, T. Huang et al., “Subtilase cytotoxin activates MAP kinases through PERK and IRE1 branches of the unfolded protein response,” Toxicological Sciences, vol. 120, no. 1, pp. 79–86, 2011. View at Publisher · View at Google Scholar · View at Scopus
  166. K. Yahiro, M. Satoh, N. Morinaga et al., “Identification of subtilase cytotoxin (SubAB) receptors whose signaling, in association with SubAB-induced BiP cleavage, is responsible for apoptosis in HeLa cells,” Infection and Immunity, vol. 79, no. 2, pp. 617–627, 2011. View at Publisher · View at Google Scholar · View at Scopus
  167. S. Sun, X. Wang, C. Wang et al., “Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells,” Planta Medica, vol. 77, no. 2, pp. 141–145, 2011. View at Publisher · View at Google Scholar · View at Scopus
  168. S. J. Choo, H. R. Park, I. J. Ryoo et al., “Deoxyverrucosidin, a novel GRP78/BiP down-regulator, produced by Penicillium sp,” Journal of Antibiotics, vol. 58, no. 3, pp. 210–213, 2005. View at Google Scholar · View at Scopus
  169. Y. Hayakawa, Y. Hattori, T. Kawasaki et al., “Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp,” Journal of Antibiotics, vol. 61, no. 6, pp. 365–371, 2008. View at Publisher · View at Google Scholar · View at Scopus
  170. I. Kozone, J. Y. Ueda, M. Takagi, and K. Shin-Ya, “JBIR-52, a new antimycin-like compound, from Streptomyces sp. ML55,” Journal of Antibiotics, vol. 62, no. 10, pp. 593–595, 2009. View at Google Scholar · View at Scopus
  171. J. H. Hwang, J. Y. Kim, M. R. Cha et al., “Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator,” Journal of Cellular Physiology, vol. 215, no. 1, pp. 243–250, 2008. View at Publisher · View at Google Scholar · View at Scopus
  172. Y. Umeda, S. Chijiwa, K. Furihata et al., “Prunustatin A, a novel GRP78 molecular chaperone down-regulator isolated from Streptomyces violaceoniger,” Journal of Antibiotics, vol. 58, no. 3, pp. 206–209, 2005. View at Google Scholar · View at Scopus
  173. D. H. Yu, J. Mcdonald, G. Liu et al., “Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy,” PLoS ONE, vol. 3, no. 12, Article ID e3951, 2008. View at Publisher · View at Google Scholar · View at Scopus
  174. S. Saito and A. Tomida, “Use of chemical genomics in assessment of the UPR,” Methods in Enzymology, vol. 491, pp. 327–341, 2011. View at Publisher · View at Google Scholar · View at Scopus
  175. I. J. Ryoo, H. R. Park, S. J. Choo et al., “Selective cytotoxic activity of valinomycin against HT-29 human colon carcinoma cells via down-regulation of GRP78,” Biological and Pharmaceutical Bulletin, vol. 29, no. 4, pp. 817–820, 2006. View at Publisher · View at Google Scholar · View at Scopus
  176. H. R. Park, A. Tomida, S. Sato et al., “Effect on tumor cells of blocking survival response to glucose deprivation,” Journal of the National Cancer Institute, vol. 96, no. 17, pp. 1300–1310, 2004. View at Publisher · View at Google Scholar · View at Scopus
  177. S. Saito, A. Furuno, J. Sakurai et al., “Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation,” Cancer Research, vol. 69, no. 10, pp. 4225–4234, 2009. View at Publisher · View at Google Scholar · View at Scopus
  178. A. J. Krentz and C. J. Bailey, “Oral antidiabetic agents: current role in type 2 diabetes mellitus,” Drugs, vol. 65, no. 3, pp. 385–411, 2005. View at Publisher · View at Google Scholar · View at Scopus
  179. M. A. Pierotti, F. Berrino, M. Gariboldi et al., “Targeting metabolism for cancer treatment and prevention: metformin, an old drug with multi-faceted effects,” Oncogene. In press.
  180. H. Noto, A. Goto, T. Tsujimoto, and M. Noda, “Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis,” PLoS ONE, vol. 7, Article ID e33411, 2012. View at Google Scholar
  181. Y. Zhou and A. S. Lee, “Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy,” Journal of the National Cancer Institute, vol. 90, no. 5, pp. 381–388, 1998. View at Google Scholar · View at Scopus
  182. M. Hong, M. Y. Lin, J. M. Huang et al., “Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation,” Journal of Biological Chemistry, vol. 280, no. 17, pp. 16821–16828, 2005. View at Publisher · View at Google Scholar · View at Scopus
  183. U. K. Mism, F. Wang, and S. V. Pizzo, “Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells,” Journal of Cellular Biochemistry, vol. 106, no. 3, pp. 381–389, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. H. A. Lim, J. H. Kim, M. K. Sung, M. K. Kim, J. H. Y. Park, and J. S. Kim, “Genistein induces glucose-regulated protein 78 in mammary tumor cells,” Journal of Medicinal Food, vol. 9, no. 1, pp. 28–32, 2006. View at Publisher · View at Google Scholar · View at Scopus
  185. T. C. Yeh, P. C. Chiang, T. K. Li et al., “Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult,” Biochemical Pharmacology, vol. 73, no. 6, pp. 782–792, 2007. View at Publisher · View at Google Scholar · View at Scopus
  186. S. P. Ermakova, B. S. Kang, B. Y. Choi et al., “(-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78,” Cancer Research, vol. 66, no. 18, pp. 9260–9269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  187. T. Luo, J. Wang, Y. Yin et al., “(-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma,” Breast Cancer Research, vol. 12, no. 1, article R8, 2010. View at Publisher · View at Google Scholar · View at Scopus
  188. Y. Li, T. Zhang, Y. Jiang, H. F. Lee, S. J. Schwartz, and D. Sun, “(-)-Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line mia paca-2,” Molecular Pharmaceutics, vol. 6, no. 4, pp. 1152–1159, 2009. View at Publisher · View at Google Scholar · View at Scopus
  189. D. G. Nagle, D. Ferreira, and Y. D. Zhou, “Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives,” Phytochemistry, vol. 67, no. 17, pp. 1849–1855, 2006. View at Publisher · View at Google Scholar · View at Scopus
  190. S. Nam, D. M. Smith, and Q. P. Dou, “Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo,” Journal of Biological Chemistry, vol. 276, no. 16, pp. 13322–13330, 2001. View at Publisher · View at Google Scholar · View at Scopus
  191. H. Tachibana, K. Koga, Y. Fujimura, and K. Yamada, “A receptor for green tea polyphenol EGCG,” Nature Structural and Molecular Biology, vol. 11, no. 4, pp. 380–381, 2004. View at Publisher · View at Google Scholar · View at Scopus
  192. O. C. Kousidou, G. N. Tzanakakis, and N. K. Karamanos, “Effects of the natural isoflavonoid genistein on growth, signaling pathways and gene expression of matrix macromolecules by breast cancer cells,” Mini-Reviews in Medicinal Chemistry, vol. 6, no. 3, pp. 331–337, 2006. View at Publisher · View at Google Scholar · View at Scopus
  193. H. Li, W. Xu, Y. Huang et al., “Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo,” International Journal of Molecular Medicine, vol. 30, pp. 1081–1086, 2012. View at Google Scholar
  194. M. H. Ravindranath, S. Muthugounder, N. Presser, and S. Viswanathan, “Anticancer therapeutic potential of soy isoflavone, genistein,” Advances in Experimental Medicine and Biology, vol. 546, pp. 121–165, 2004. View at Google Scholar · View at Scopus
  195. B. Martin-Castillo, A. Vazquez-Martin, C. Oliveras-Ferraros, and J. A. Menendez, “Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena,” Cell Cycle, vol. 9, no. 6, pp. 1057–1064, 2010. View at Google Scholar · View at Scopus
  196. M. Y. El-Mir, V. Nogueira, E. Fontaine, N. Avéret, M. Rigoulet, and X. Leverve, “Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I,” Journal of Biological Chemistry, vol. 275, no. 1, pp. 223–228, 2000. View at Publisher · View at Google Scholar · View at Scopus
  197. M. R. Owen, E. Doran, and A. P. Halestrap, “Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain,” Biochemical Journal, vol. 348, no. 3, pp. 607–614, 2000. View at Publisher · View at Google Scholar · View at Scopus
  198. A. Delpino and M. Castelli, “The 78 kda glucose-regulated protein (GRP78/BIP) is expressed on the cell membrane, is released into cell culture medium and is also present in human peripheral circulation,” Bioscience Reports, vol. 22, no. 3-4, pp. 407–420, 2002. View at Publisher · View at Google Scholar · View at Scopus
  199. D. J. Davidson, C. Haskell, S. Majest et al., “Kringle 5 of human plasminogen induces apoptosis of endothelial and tumor cells through surface-expressed glucose-regulated protein 78,” Cancer Research, vol. 65, no. 11, pp. 4663–4672, 2005. View at Publisher · View at Google Scholar · View at Scopus
  200. K. Miharada, G. Karlsson, M. Rehn et al., “Cripto regulates hematopoietic stem cells as a hypoxic-niche-related factor through cell surface receptor GRP78,” Cell Stem Cell, vol. 9, pp. 330–344, 2011. View at Google Scholar
  201. U. K. Misra, R. Deedwania, and S. V. Pizzo, “Binding of activated α2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK,” Journal of Biological Chemistry, vol. 280, no. 28, pp. 26278–26286, 2005. View at Publisher · View at Google Scholar · View at Scopus
  202. U. K. Misra and S. V. Pizzo, “Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of α2-macroglobulin to 1-LN prostate cancer cells,” Cellular Signalling, vol. 16, no. 4, pp. 487–496, 2004. View at Publisher · View at Google Scholar · View at Scopus
  203. G. G. de Ridder, M. Gonzalez-Gronow, R. Ray, and S. V. Pizzo, “Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma,” Melanoma Research, vol. 21, no. 1, pp. 35–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  204. G. G. de Ridder, R. Ray, and S. V. Pizzo, “A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice,” Melanoma Research, vol. 22, pp. 225–235, 2012. View at Google Scholar
  205. U. K. Misra and S. V. Pizzo, “Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells,” Cancer Biology and Therapy, vol. 9, no. 2, pp. 142–152, 2010. View at Google Scholar · View at Scopus
  206. R. Ray, G. G. de Ridder, J. P. Eu et al., “The Escherichia coli subtilase cytotoxin a subunit specifically cleaves cell-surface GRP78 and abolishes COOH-terminal-dependent signaling,” The Journal of Biological Chemistry, vol. 287, pp. 32755–32769, 2012. View at Google Scholar
  207. S. Thomas, N. Sharma, E. B. Golden et al., “Preferential killing of triple-negative breast cancer cells in vitro and in vivo when pharmacological aggravators of endoplasmic reticulum stress are combined with autophagy inhibitors,” Cancer Letters, vol. 325, pp. 63–71, 2012. View at Google Scholar
  208. H. L. Pahl, “Signal transduction from the endoplasmic reticulum to the cell nucleus,” Physiological Reviews, vol. 79, no. 3, pp. 683–701, 1999. View at Google Scholar · View at Scopus
  209. M. Treiman, C. Caspersen, and S. B. Christensen, “A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca2+-ATPases,” Trends in Pharmacological Sciences, vol. 19, no. 4, pp. 131–135, 1998. View at Publisher · View at Google Scholar · View at Scopus
  210. A. M. L. Winther, H. Liu, Y. Sonntag et al., “Critical roles of hydrophobicity and orientation of side chains for inactivation of sarcoplasmic reticulum Ca2+-ATPase with thapsigargin and thapsigargin analogs,” Journal of Biological Chemistry, vol. 285, no. 37, pp. 28883–28892, 2010. View at Publisher · View at Google Scholar · View at Scopus
  211. H. Hakii, H. Fujiki, and M. Suganuma, “Thapsigargin, a histamine secretagogue, is a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter in two-stage mouse skin carcinogenesis,” Journal of Cancer Research and Clinical Oncology, vol. 111, no. 3, pp. 177–181, 1986. View at Google Scholar · View at Scopus
  212. K. Ohuchi, C. Takahashi, N. Hirasawa, M. Watanabe, H. Fujiki, and S. Tsurufuji, “Stimulation of histamine release and arachidonic acid metabolism in rat peritonel mast cells by thapsigargin a non-TPA-type tumor promoter,” Biochimica et Biophysica Acta, vol. 1003, no. 1, pp. 9–14, 1989. View at Google Scholar · View at Scopus
  213. S. R. Denmeade, C. M. Jakobsen, S. Janssen et al., “Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer,” Journal of the National Cancer Institute, vol. 95, no. 13, pp. 990–1000, 2003. View at Google Scholar · View at Scopus
  214. S. R. Denmeade, A. M. Mhaka, D. M. Rosen et al., “Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy,” Science Translational Medicine, vol. 4, no. 140, Article ID 140ra86, 2012. View at Google Scholar
  215. J. Adams and M. Kauffman, “Development of the proteasome inhibitor Velcade (Bortezomib),” Cancer Investigation, vol. 22, no. 2, pp. 304–311, 2004. View at Publisher · View at Google Scholar · View at Scopus
  216. D. Chauhan, T. Hideshima, and K. C. Anderson, “Proteasome inhibition in multiple myeloma: therapeutic implication,” Annual Review of Pharmacology and Toxicology, vol. 45, pp. 465–476, 2005. View at Publisher · View at Google Scholar · View at Scopus
  217. A. Fribley, Q. Zeng, and C. Y. Wang, “Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells,” Molecular and Cellular Biology, vol. 24, no. 22, pp. 9695–9704, 2004. View at Publisher · View at Google Scholar · View at Scopus
  218. S. T. Nawrocki, J. S. Carew, M. S. Pino et al., “Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis,” Cancer Research, vol. 65, no. 24, pp. 11658–11666, 2005. View at Publisher · View at Google Scholar · View at Scopus
  219. E. A. Obeng, L. M. Carlson, D. M. Gutman, W. J. Harrington, K. P. Lee, and L. H. Boise, “Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells,” Blood, vol. 107, no. 12, pp. 4907–4916, 2006. View at Publisher · View at Google Scholar · View at Scopus
  220. S. Meister, U. Schubert, K. Neubert et al., “Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition,” Cancer Research, vol. 67, no. 4, pp. 1783–1792, 2007. View at Publisher · View at Google Scholar · View at Scopus
  221. G. Bianchi, L. Oliva, P. Cascio et al., “The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition,” Blood, vol. 113, no. 13, pp. 3040–3049, 2009. View at Publisher · View at Google Scholar · View at Scopus
  222. D. R. Carrasco, K. Sukhdeo, M. Protopopova et al., “"The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis,” Cancer Cell, vol. 11, no. 4, pp. 349–360, 2007. View at Publisher · View at Google Scholar · View at Scopus
  223. Y. Shen and L. M. Hendershot, “Identification of ERdj3 and OBF-1/BOB-1/OCA-B as direct targets of XBP-1 during plasma cell differentiation,” Journal of Immunology, vol. 179, no. 5, pp. 2969–2978, 2007. View at Google Scholar · View at Scopus
  224. S. Chen, X. Liu, P. Yue, A. H. Schönthal, F. R. Khuri, and S. Y. Sun, “CCAAT/enhancer binding protein homologous protein-dependent death receptor 5 induction and ubiquitin/proteasome-mediated cellular FLICE-inhibitory protein down-regulation contribute to enhancement of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by dimethyl-celecoxib in human non-small-cell lung cancer cells,” Molecular Pharmacology, vol. 72, no. 5, pp. 1269–1279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  225. T. Hideshima, H. Ikeda, D. Chauhan et al., “Bortezomib induces canonical nuclear factor-κB activation in multiple myeloma cells,” Blood, vol. 114, no. 5, pp. 1046–1052, 2009. View at Publisher · View at Google Scholar · View at Scopus
  226. T. Hideshima, C. Mitsiades, M. Akiyama et al., “Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341,” Blood, vol. 101, no. 4, pp. 1530–1534, 2003. View at Publisher · View at Google Scholar · View at Scopus
  227. J. Li, B. Lee, and A. S. Lee, “Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-UP-regulated modulator of apoptosis (PUMA) and NOXA by p53,” Journal of Biological Chemistry, vol. 281, no. 11, pp. 7260–7270, 2006. View at Publisher · View at Google Scholar · View at Scopus
  228. E. Szegezdi, S. E. Logue, A. M. Gorman, and A. Samali, “Mediators of endoplasmic reticulum stress-induced apoptosis,” EMBO Reports, vol. 7, no. 9, pp. 880–885, 2006. View at Publisher · View at Google Scholar · View at Scopus
  229. C. M. Perry, J. E. Frampton, P. L. McCormack, M. A. A. Siddiqui, and R. S. Cvetković, “Nelfinavir: a review of its use in the management of HIV infection,” Drugs, vol. 65, no. 15, pp. 2209–2244, 2005. View at Publisher · View at Google Scholar · View at Scopus
  230. M. Piccinini, M. T. Rinaudo, A. Anselmino et al., “The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV reverse transcriptase inhibitors, adversely affect human proteasome function,” Antiviral Therapy, vol. 10, no. 2, pp. 215–223, 2005. View at Google Scholar · View at Scopus
  231. W. Jiang, P. J. Mikochik, J. H. Ra et al., “HIV protease inhibitor nelfinavir inhibits growth of human melanoma cells by induction of cell cycle arrest,” Cancer Research, vol. 67, no. 3, pp. 1221–1227, 2007. View at Publisher · View at Google Scholar · View at Scopus
  232. J. J. Gills, J. LoPiccolo, J. Tsurutani et al., “Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and invivo,” Clinical Cancer Research, vol. 13, no. 17, pp. 5183–5194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  233. P. Pyrko, A. Kardosh, W. Wang, W. Xiong, A. H. Schönthal, and T. C. Chen, “HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress,” Cancer Research, vol. 67, no. 22, pp. 10920–10928, 2007. View at Publisher · View at Google Scholar · View at Scopus
  234. A. Brüning, P. Burger, M. Vogel et al., “Nelfinavir induces the unfolded protein response in ovarian cancer cells, resulting in ER vacuolization, cell cycle retardation and apoptosis,” Cancer Biology & Therapy, vol. 8, no. 3, pp. 226–232, 2009. View at Google Scholar · View at Scopus
  235. A. K. Gupta, B. Li, G. J. Cerniglia, M. S. Ahmed, S. M. Hahn, and A. Maity, “The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response,” Neoplasia, vol. 9, no. 4, pp. 271–278, 2007. View at Publisher · View at Google Scholar · View at Scopus
  236. A. Brüning, K. Friese, A. Burges, and I. Mylonas, “Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells,” Breast Cancer Research, vol. 12, no. 4, article R45, 2010. View at Publisher · View at Google Scholar · View at Scopus
  237. A. Brüning, M. Vogel, P. Burger et al., “Nelfinavir induces TRAIL receptor upregulation in ovarian cancer cells,” Biochemical and Biophysical Research Communications, vol. 377, no. 4, pp. 1309–1314, 2008. View at Publisher · View at Google Scholar · View at Scopus
  238. X. Tian, J. Ye, M. Alonso-Basanta et al., “Modulation of CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 expression by nelfinavir sensitizes glioblastoma multiforme cells to tumor necrosis factor-related apoptosisinducing ligand (TRAIL),” Journal of Biological Chemistry, vol. 286, pp. 29408–29416, 2011. View at Google Scholar
  239. K. C. Cuneo, T. Tu, L. Geng, A. Fu, D. E. Hallahan, and C. D. Willey, “HIV protease inhibitors enhance the efficacy of irradiation,” Cancer Research, vol. 67, no. 10, pp. 4886–4893, 2007. View at Publisher · View at Google Scholar · View at Scopus
  240. A. K. Gupta, G. J. Cerniglia, R. Mick, W. G. McKenna, and R. J. Muschel, “HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo,” Cancer Research, vol. 65, no. 18, pp. 8256–8265, 2005. View at Publisher · View at Google Scholar · View at Scopus
  241. J. Zeng, A. P. See, K. Aziz et al., “Nelfinavir induces radiation sensitization in pituitary adenoma cells,” Cancer Biology & Therapy, vol. 12, pp. 657–663, 2011. View at Google Scholar
  242. W. B. Bernstein and P. A. Dennis, “Repositioning HIV protease inhibitors as cancer therapeutics,” Current Opinion in HIV and AIDS, vol. 3, no. 6, pp. 666–675, 2008. View at Publisher · View at Google Scholar · View at Scopus
  243. A. Brüning, A. Gingelmaier, K. Friese, and I. Mylonas, “New prospects for nelfinavir in non-HIV-related diseases,” Current Molecular Pharmacology, vol. 3, no. 2, pp. 91–97, 2010. View at Publisher · View at Google Scholar · View at Scopus
  244. A. T. Koki and J. L. Masferrer, “Celecoxib: a specific COX-2 inhibitor with anticancer properties,” Cancer Control, vol. 9, no. 2, pp. 28–35, 2002. View at Google Scholar · View at Scopus
  245. S. Grösch, T. J. Maier, S. Schiffmann, and G. Geisslinger, “Cyclooxygenase-2 (COX-2)—independent anticarcinogenic effects of selective COX-2 inhibitors,” Journal of the National Cancer Institute, vol. 98, no. 11, pp. 736–747, 2006. View at Publisher · View at Google Scholar · View at Scopus
  246. A. H. Schönthal, “Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy,” British Journal of Cancer, vol. 97, no. 11, pp. 1465–1468, 2007. View at Publisher · View at Google Scholar · View at Scopus
  247. K. Kashfi and B. Rigas, “Non-COX-2 targets and cancer: expanding the molecular target repertoire of chemoprevention,” Biochemical Pharmacology, vol. 70, no. 7, pp. 969–986, 2005. View at Publisher · View at Google Scholar · View at Scopus
  248. J. F. Knudsen, U. Carlsson, P. Hammarström, G. H. Sokol, and L. R. Cantilena, “The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II,” Inflammation, vol. 28, no. 5, pp. 285–290, 2004. View at Publisher · View at Google Scholar · View at Scopus
  249. A. Weber, A. Casini, A. Heine et al., “Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition,” Journal of Medicinal Chemistry, vol. 47, no. 3, pp. 550–557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  250. A. J. Johnson, A. L. Hsu, H. P. Lin, X. Song, and C. S. Chen, “The cyclo-oxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulum Ca2+-ATPases: a plausible link with its anti-tumour effect and cardiovascular risks,” Biochemical Journal, vol. 366, no. 3, pp. 831–837, 2002. View at Publisher · View at Google Scholar · View at Scopus
  251. S. H. Kim, C. I. Hwang, W. Y. Park, Y. S. Juhnn, J. H. Lee, and Y. S. Song, “Erratum: GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells,” Carcinogenesis, vol. 28, no. 1, pp. 223–231, 2007. View at Publisher · View at Google Scholar · View at Scopus
  252. P. Pyrko, A. Kardosh, Y. T. Liu et al., “Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib,” Molecular Cancer Therapeutics, vol. 6, no. 4, pp. 1262–1275, 2007. View at Publisher · View at Google Scholar · View at Scopus
  253. S. Tsutsumi, T. Gotoh, W. Tomisato et al., “Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis,” Cell Death and Differentiation, vol. 11, no. 9, pp. 1009–1016, 2004. View at Publisher · View at Google Scholar · View at Scopus
  254. S. Tsutsumi, T. Namba, K. I. Tanaka et al., “Celecoxib upregulates endoplasmic reticulum chaperones that inhibit celecoxib-induced apoptosis in human gastric cells,” Oncogene, vol. 25, no. 7, pp. 1018–1029, 2006. View at Publisher · View at Google Scholar · View at Scopus
  255. P. Pyrko, A. Kardosh, and A. H. Schönthal, “Celecoxib transiently inhibits cellular protein synthesis,” Biochemical Pharmacology, vol. 75, no. 2, pp. 395–404, 2008. View at Publisher · View at Google Scholar · View at Scopus
  256. J. Zhu, J. W. Huang, P. H. Tseng et al., “From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors,” Cancer Research, vol. 64, no. 12, pp. 4309–4318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  257. J. Zhu, X. Song, H. P. Lin et al., “Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents,” Journal of the National Cancer Institute, vol. 94, no. 23, pp. 1745–1757, 2002. View at Google Scholar · View at Scopus
  258. A. Kardosh, N. Soriano, Y. T. Liu et al., “Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib,” Blood, vol. 106, no. 13, pp. 4330–4338, 2005. View at Publisher · View at Google Scholar · View at Scopus
  259. A. Kardosh, W. Wang, J. Uddin et al., “Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo,” Cancer Biology and Therapy, vol. 4, no. 5, pp. 571–582, 2005. View at Google Scholar · View at Scopus
  260. S. K. Kulp, Y. T. Yang, C. C. Hung et al., “3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells,” Cancer Research, vol. 64, no. 4, pp. 1444–1451, 2004. View at Publisher · View at Google Scholar · View at Scopus
  261. P. Pyrko, N. Soriano, A. Kardosh et al., “Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo,” Molecular Cancer, vol. 5, article 19, 2006. View at Publisher · View at Google Scholar · View at Scopus
  262. X. Song, H. P. Lin, A. J. Johnson et al., “Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells,” Journal of the National Cancer Institute, vol. 94, no. 8, pp. 585–591, 2002. View at Google Scholar · View at Scopus
  263. N. Kusunoki, T. Ito, N. Sakurai, H. Handa, and S. Kawai, “A celecoxib derivative potently inhibits proliferation of colon adenocarcinoma cells by induction of apoptosis,” Anticancer Research, vol. 26, no. 5 A, pp. 3229–3236, 2006. View at Google Scholar · View at Scopus
  264. N. Kusunoki, T. Ito, N. Sakurai, T. Suguro, H. Handa, and S. Kawai, “A novel celecoxib derivative potently induces apoptosis of human synovial fibroblasts,” Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 2, pp. 796–803, 2005. View at Publisher · View at Google Scholar · View at Scopus
  265. I. Alloza, A. Baxter, Q. Chen, R. Matthiesen, and K. Vandenbroeck, “Celecoxib inhibits interleukin-12 αβ and β2 folding and secretion by a novel COX2-independent mechanism involving chaperones of the endoplasmic reticulum,” Molecular Pharmacology, vol. 69, no. 5, pp. 1579–1587, 2006. View at Publisher · View at Google Scholar · View at Scopus
  266. M. McLaughlin, I. Alloza, H. P. Quoc, C. J. Scott, Y. Hirabayashi, and K. Vandenbroeck, “Inhibition of secretion of interleukin (IL)-12/IL-23 family cytokines by 4-trifluoromethyl-celecoxib is coupled to degradation via the endoplasmic reticulum stress protein HERP,” Journal of Biological Chemistry, vol. 285, no. 10, pp. 6960–6969, 2010. View at Publisher · View at Google Scholar · View at Scopus
  267. H. Ding, C. Han, D. Guo et al., “Sensitivity to the non-COX inhibiting celecoxib derivative, OSU03012, is p21WAF1/CIP1 dependent,” International Journal of Cancer, vol. 123, no. 12, pp. 2931–2938, 2008. View at Publisher · View at Google Scholar · View at Scopus
  268. A. J. Johnson, L. L. Smith, J. Zhu et al., “A novel celecoxib derivative, OSU03012, induces cytotoxicity in primary CLL cells and transformed B-cell lymphoma cell line via a caspase- and Bcl-2-independent mechanism,” Blood, vol. 105, no. 6, pp. 2504–2509, 2005. View at Publisher · View at Google Scholar · View at Scopus
  269. E. P. Ryan, T. P. Bushnell, A. E. Friedman, I. Rahman, and R. P. Phipps, “Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells,” Cancer Immunology, Immunotherapy, vol. 57, no. 3, pp. 347–358, 2008. View at Publisher · View at Google Scholar · View at Scopus
  270. H. C. Chuang, A. Kardosh, K. J. Gaffney, N. A. Petasis, and A. H. Schönthal, “COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro,” Molecular Cancer, vol. 7, article 38, 2008. View at Publisher · View at Google Scholar · View at Scopus
  271. S. T. Chen, S. Thomas, K. J. Gaffney, S. G. Louie, N. A. Petasis, and A. H. Schönthal, “Cytotoxic effects of celecoxib on Raji lymphoma cells correlate with aggravated endoplasmic reticulum stress but not with inhibition of cyclooxygenase-2,” Leukemia Research, vol. 34, no. 2, pp. 250–253, 2010. View at Publisher · View at Google Scholar · View at Scopus
  272. L. Booth, S. C. Cazanave, H. A. Hamed et al., “OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing,” Cancer Biology & Therapy, vol. 13, pp. 224–236, 2012. View at Google Scholar
  273. H. A. Hamed, A. Yacoub, M. A. Park et al., “OSU-03012 enhances Ad.mda-7-induced GBM cell killing via ER stress and autophagy and by decreasing expression of mitochondrial protective proteins,” Cancer Biology and Therapy, vol. 9, no. 7, pp. 526–536, 2010. View at Google Scholar · View at Scopus
  274. A. Yacoub, M. A. Park, D. Hanna et al., “OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF-dependent killing of transformed cells,” Molecular Pharmacology, vol. 70, no. 2, pp. 589–603, 2006. View at Publisher · View at Google Scholar · View at Scopus
  275. H. Y. Cho, S. Thomas, E. B. Golden et al., “Enhanced killing of chemo-resistant breast cancer cells via controlled aggravation of ER stress,” Cancer Letters, vol. 282, no. 1, pp. 87–97, 2009. View at Publisher · View at Google Scholar · View at Scopus
  276. N. Arber, C. J. Eagle, J. Spicak et al., “Celecoxib for the prevention of colorectal adenomatous polyps,” The New England Journal of Medicine, vol. 355, no. 9, pp. 885–895, 2006. View at Publisher · View at Google Scholar · View at Scopus
  277. M. M. Bertagnolli, C. J. Eagle, A. G. Zauber et al., “Celecoxib for the prevention of sporadic colorectal adenomas,” The New England Journal of Medicine, vol. 355, no. 9, pp. 873–884, 2006. View at Publisher · View at Google Scholar · View at Scopus
  278. G. Steinbach, P. M. Lynch, R. K. S. Phillips et al., “The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis,” The New England Journal of Medicine, vol. 342, no. 26, pp. 1946–1952, 2000. View at Publisher · View at Google Scholar · View at Scopus
  279. L. C. A. Cerchietti, M. R. Bonomi, A. H. Navigante, M. A. Castro, M. E. Cabalar, and B. M. C. Roth, “Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases,” Journal of Neuro-Oncology, vol. 71, no. 1, pp. 73–81, 2005. View at Publisher · View at Google Scholar · View at Scopus
  280. C. H. Crane, K. Mason, N. A. Janjan, and L. Milas, “Initial experience combining cyclooxygenase-2 inhibition with chemoradiation for locally advanced pancreatic cancer,” American Journal of Clinical Oncology, vol. 26, no. 4, pp. S81–S84, 2003. View at Publisher · View at Google Scholar · View at Scopus
  281. S. M. Gadgeel, J. C. Ruckdeschel, E. I. Heath, L. K. Heilbrun, R. Venkatramanamoorthy, and A. Wozniak, “Phase II study of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in patients with platinum refractory non-small cell lung cancer (NSCLC),” Journal of Thoracic Oncology, vol. 2, no. 4, pp. 299–305, 2007. View at Publisher · View at Google Scholar · View at Scopus
  282. D. K. Gaffney, K. Winter, A. P. Dicker et al., “A Phase II study of acute toxicity for Celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG 0128,” International Journal of Radiation Oncology Biology Physics, vol. 67, no. 1, pp. 104–109, 2007. View at Publisher · View at Google Scholar · View at Scopus
  283. C. Gridelli, C. Gallo, A. Ceribelli et al., “Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study,” The Lancet Oncology, vol. 8, no. 6, pp. 500–512, 2007. View at Publisher · View at Google Scholar · View at Scopus
  284. Z. Liao, R. Komaki, L. Milas et al., “A phase I clinical trial of thoracic radiotherapy and concurrent celecoxib for patients with unfavorable performance status inoperable/unresectable non-small cell lung cancer,” Clinical Cancer Research, vol. 11, no. 9, pp. 3342–3348, 2005. View at Publisher · View at Google Scholar · View at Scopus
  285. K. J. O'Byrne, S. Danson, D. Dunlop et al., “Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 25, no. 22, pp. 3266–3273, 2007. View at Publisher · View at Google Scholar · View at Scopus
  286. D. A. Reardon, J. A. Quinn, J. Vredenburgh et al., “Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma,” Cancer, vol. 103, no. 2, pp. 329–338, 2005. View at Publisher · View at Google Scholar · View at Scopus
  287. M. R. Smith, J. Manola, D. S. Kaufman, W. K. Oh, G. J. Bubley, and P. W. Kantoff, “Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy,” Journal of Clinical Oncology, vol. 24, no. 18, pp. 2723–2728, 2006. View at Publisher · View at Google Scholar · View at Scopus
  288. S. Oyadomari, A. Koizumi, K. Takeda et al., “Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes,” Journal of Clinical Investigation, vol. 109, no. 4, pp. 525–532, 2002. View at Publisher · View at Google Scholar · View at Scopus
  289. Y. Li, R. F. Schwabe, T. DeVries-Seimon et al., “Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-α and interleukin-6: model of NF-κB- and map kinase-dependent inflammation in advanced atherosclerosis,” Journal of Biological Chemistry, vol. 280, no. 23, pp. 21763–21772, 2005. View at Publisher · View at Google Scholar · View at Scopus
  290. X. Kedi, Y. Ming, W. Yongping, Y. Yi, and Z. Xiaoxiang, “Free cholesterol overloading induced smooth muscle cells death and activated both ER- and mitochondrial-dependent death pathway,” Atherosclerosis, vol. 207, no. 1, pp. 123–130, 2009. View at Publisher · View at Google Scholar · View at Scopus
  291. H. Tsukano, T. Gotoh, M. Endo et al., “The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 10, pp. 1925–1932, 2010. View at Publisher · View at Google Scholar · View at Scopus
  292. E. Thorp, G. Li, T. A. Seimon, G. Kuriakose, D. Ron, and I. Tabas, “Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP,” Cell Metabolism, vol. 9, no. 5, pp. 474–481, 2009. View at Publisher · View at Google Scholar · View at Scopus
  293. M. Sanson, N. Augé, C. Vindis et al., “Oxidized low-density lipoproteins trigger endoplasmic reticulum stress in vascular cells: prevention by oxygen-regulated protein 150 expression,” Circulation Research, vol. 104, no. 3, pp. 328–336, 2009. View at Publisher · View at Google Scholar · View at Scopus
  294. G. H. Werstuck, M. I. Khan, G. Femia et al., “Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model,” Diabetes, vol. 55, no. 1, pp. 93–101, 2006. View at Publisher · View at Google Scholar · View at Scopus
  295. I. Tabas, “The role of endoplasmic reticulum stress in the progression of atherosclerosis,” Circulation Research, vol. 107, no. 7, pp. 839–850, 2010. View at Publisher · View at Google Scholar · View at Scopus
  296. H. L. Kammoun, H. Chabanon, I. Hainault et al., “GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice,” Journal of Clinical Investigation, vol. 119, no. 5, pp. 1201–1215, 2009. View at Publisher · View at Google Scholar · View at Scopus
  297. G. H. Werstuck, S. R. Lentz, S. Dayal et al., “Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways,” Journal of Clinical Investigation, vol. 107, no. 10, pp. 1263–1273, 2001. View at Google Scholar · View at Scopus
  298. M. J. Pagliassotti, “Endoplasmic reticulum stress in nonalcoholic fatty liver disease,” Annual Review of Nutrition, vol. 32, pp. 17–33, 2012. View at Google Scholar
  299. D. Imrie and K. C. Sadler, “Stress management: how the unfolded protein response impacts fatty liver disease,” Journal of Hepatology, vol. 57, pp. 1147–1151, 2012. View at Google Scholar
  300. C. Ji, R. Mehrian-Shai, C. Chan, Y. H. Hsu, and N. Kaplowitz, “Role of CHOP in hepatic apoptosis in the murine model of intragastric ethanol feeding,” Alcoholism, vol. 29, no. 8, pp. 1496–1503, 2005. View at Publisher · View at Google Scholar · View at Scopus
  301. N. Kaplowitz, A. T. Tin, M. Shinohara, and C. Ji, “Endoplasmic reticulum stress and liver injury,” Seminars in Liver Disease, vol. 27, no. 4, pp. 367–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  302. C. C. Glembotski, “The role of the unfolded protein response in the heart,” Journal of Molecular and Cellular Cardiology, vol. 44, no. 3, pp. 453–459, 2008. View at Publisher · View at Google Scholar · View at Scopus
  303. K. I. Okada, T. Minamino, Y. Tsukamoto et al., “Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis,” Circulation, vol. 110, no. 6, pp. 705–712, 2004. View at Publisher · View at Google Scholar · View at Scopus
  304. D. J. Thuerauf, M. Marcinko, N. Gude, M. Rubio, M. A. Sussman, and C. C. Glembotski, “Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes,” Circulation Research, vol. 99, no. 3, pp. 275–282, 2006. View at Publisher · View at Google Scholar · View at Scopus
  305. K. Shintani-Ishida, M. Nakajima, K. Uemura, and K. I. Yoshida, “Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP78,” Biochemical and Biophysical Research Communications, vol. 345, no. 4, pp. 1600–1605, 2006. View at Publisher · View at Google Scholar · View at Scopus
  306. Y. X. Pan, L. Lin, A. J. Ren et al., “HSP70 and GRP78 induced by endothelin-1 pretreatment enhance tolerance to hypoxia in cultured neonatal rat cardiomyocytes,” Journal of Cardiovascular Pharmacology, vol. 44, supplement 1, pp. S117–S120, 2004. View at Publisher · View at Google Scholar · View at Scopus
  307. M. Vitadello, D. Penzo, V. Petronilli et al., “Overexpression of the stress protein Grp94 reduces cardiomyocyte necrosis due to calcium overload and simulated ischemia,” The FASEB Journal, vol. 17, no. 8, pp. 923–925, 2003. View at Google Scholar · View at Scopus
  308. J. Groenendyk, P. K. Sreenivasaiah, D. H. Kim, L. B. Agellon, and M. Michalak, “Biology of endoplasmic reticulum stress in the heart,” Circulation Research, vol. 107, no. 10, pp. 1185–1197, 2010. View at Publisher · View at Google Scholar · View at Scopus
  309. K. D. Tardif, K. Mori, R. J. Kaufman, and A. Siddiqui, “Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response,” Journal of Biological Chemistry, vol. 279, no. 17, pp. 17158–17164, 2004. View at Publisher · View at Google Scholar · View at Scopus
  310. Z. Xu, G. Jensen, and T. S. Yen, “Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum,” Journal of Virology, vol. 71, no. 10, pp. 7387–7392, 1997. View at Google Scholar · View at Scopus
  311. G. Waris, K. D. Tardif, and A. Siddiqui, “Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-κB and STAT-3,” Biochemical Pharmacology, vol. 64, no. 10, pp. 1425–1430, 2002. View at Publisher · View at Google Scholar · View at Scopus
  312. H. C. Wang, W. Huang, M. D. Lai, and I. J. Su, “Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis,” Cancer Science, vol. 97, no. 8, pp. 683–688, 2006. View at Publisher · View at Google Scholar · View at Scopus
  313. U. Unterberger, R. Höftberger, E. Gelpi, H. Flicker, H. Budka, and T. Voigtländer, “Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo,” Journal of Neuropathology and Experimental Neurology, vol. 65, no. 4, pp. 348–357, 2006. View at Publisher · View at Google Scholar · View at Scopus
  314. T. Katayama, K. Imaizumi, N. Sato et al., “Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response,” Nature Cell Biology, vol. 1, no. 8, pp. 479–485, 1999. View at Google Scholar · View at Scopus
  315. O. Milhavet, J. L. Martindale, S. Camandola et al., “Involvement of Gadd153 in the pathogenic action of presenilin-1 mutations,” Journal of Neurochemistry, vol. 83, no. 3, pp. 673–681, 2002. View at Publisher · View at Google Scholar · View at Scopus
  316. M. Niwa, C. Sidrauski, R. J. Kaufman, and P. Walter, “A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response,” Cell, vol. 99, no. 7, pp. 691–702, 1999. View at Google Scholar · View at Scopus
  317. S. Bernales, M. M. Soto, and E. McCullagh, “Unfolded protein stress in the endoplasmic reticulum and mitochondria: a role in neurodegeneration,” Frontiers in Aging Neuroscience, vol. 4, article 5, 2012. View at Google Scholar
  318. K. M. Doyle, D. Kennedy, A. M. Gorman et al., “Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders,” Journal of Cellular and Molecular Medicine, vol. 15, pp. 2025–2039, 2011. View at Google Scholar
  319. Y. Imai, M. Soda, and R. Takahashi, “Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity,” Journal of Biological Chemistry, vol. 275, no. 46, pp. 35661–35664, 2000. View at Publisher · View at Google Scholar · View at Scopus
  320. T. M. Dawson and V. L. Dawson, “Molecular pathways of neurodegeneration in Parkinson's disease,” Science, vol. 302, no. 5646, pp. 819–822, 2003. View at Publisher · View at Google Scholar · View at Scopus
  321. L. Bouman, A. Schlierf, A. K. Lutz et al., “Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress,” Cell Death and Differentiation, vol. 18, no. 5, pp. 769–782, 2011. View at Publisher · View at Google Scholar · View at Scopus
  322. Y. Kouroku, E. Fujita, A. Jimbo et al., “Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation,” Human Molecular Genetics, vol. 11, no. 13, pp. 1505–1515, 2002. View at Google Scholar · View at Scopus
  323. A. Zuleta, R. L. Vidal, D. Armentano et al., “AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington's disease,” Biochemical and Biophysical Research Communications, vol. 420, pp. 558–563, 2012. View at Google Scholar
  324. J. Y. Noh, H. Lee, S. Song et al., “SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition,” Journal of Biological Chemistry, vol. 284, no. 17, pp. 11318–11325, 2009. View at Publisher · View at Google Scholar · View at Scopus
  325. A. Carnemolla, E. Fossale, E. Agostoni et al., “Rrs1 is involved in endoplasmic reticulum stress response in huntington disease,” Journal of Biological Chemistry, vol. 284, no. 27, pp. 18167–18173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  326. H. Lee, J. Y. Noh, Y. Oh et al., “IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux,” Human Molecular Genetics, vol. 21, pp. 101–114, 2012. View at Google Scholar
  327. M. R. Fernandez-Fernandez, I. Ferrer, and J. J. Lucas, “Impaired ATF6α processing, decreased Rheb and neuronal cell cycle re-entry in Huntington's disease,” Neurobiology of Disease, vol. 41, no. 1, pp. 23–32, 2011. View at Publisher · View at Google Scholar · View at Scopus
  328. S. Saxena, E. Cabuy, and P. Caroni, “A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice,” Nature Neuroscience, vol. 12, no. 5, pp. 627–636, 2009. View at Publisher · View at Google Scholar · View at Scopus
  329. H. Nishitoh, H. Kadowaki, A. Nagai et al., “ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1,” Genes and Development, vol. 22, no. 11, pp. 1451–1464, 2008. View at Publisher · View at Google Scholar · View at Scopus
  330. J. D. Atkin, M. A. Farg, A. K. Walker, C. McLean, D. Tomas, and M. K. Horne, “Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis,” Neurobiology of Disease, vol. 30, no. 3, pp. 400–407, 2008. View at Publisher · View at Google Scholar · View at Scopus
  331. C. Hetz, M. Russelakis-Carneiro, K. Maundrell, J. Castilla, and C. Soto, “Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein,” The EMBO Journal, vol. 22, no. 20, pp. 5435–5445, 2003. View at Publisher · View at Google Scholar · View at Scopus
  332. C. Hetz, M. Russelakis-Carneiro, S. Wälchli et al., “The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity,” Journal of Neuroscience, vol. 25, no. 11, pp. 2793–2802, 2005. View at Publisher · View at Google Scholar · View at Scopus
  333. S. B. Wang, Q. Shi, Y. Xu et al., “Protein disulfide isomerase regulates endoplasmic reticulum stress and the apoptotic process during prion infection and PrP mutantinduced cytotoxicity,” PLoS ONE, vol. 7, Article ID e38221, 2012. View at Google Scholar
  334. K. Xu and X. P. Zhu, “Endoplasmic reticulum stress and prion diseases,” Reviews in the Neurosciences, vol. 23, pp. 79–84, 2012. View at Google Scholar
  335. C. Jamora, G. Dennert, and A. S. Lee, “Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 15, pp. 7690–7694, 1996. View at Publisher · View at Google Scholar · View at Scopus
  336. M. Shuda, N. Kondoh, N. Imazeki et al., “Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis,” Journal of Hepatology, vol. 38, no. 5, pp. 605–614, 2003. View at Publisher · View at Google Scholar · View at Scopus
  337. A. H. Schönthal, “Targeting endoplasmic reticulum stress for cancer therapy,” Frontiers in Bioscience, vol. 4, pp. 412–431, 2012. View at Google Scholar
  338. S. E. Choi, Y. J. Lee, H. J. Jang et al., “A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS),” Archives of Biochemistry and Biophysics, vol. 475, no. 2, pp. 109–114, 2008. View at Publisher · View at Google Scholar · View at Scopus
  339. Y. Y. Lee, S. H. Hong, Y. J. Lee et al., “Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress,” Biochemical and Biophysical Research Communications, vol. 397, no. 4, pp. 735–739, 2010. View at Publisher · View at Google Scholar · View at Scopus
  340. R. Lenin, M. S. Maria, M. Agrawal et al., “Amelioration of glucolipotoxicity-induced endoplasmic reticulum stress by a, “chemical chaperone” in human THP-1 monocytes,” Experimental Diabetes Research, vol. 2012, Article ID 356487, 10 pages, 2012. View at Google Scholar
  341. Q. Xie, V. I. Khaoustov, C. C. Chung et al., “Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation,” Hepatology, vol. 36, no. 3, pp. 592–601, 2002. View at Publisher · View at Google Scholar · View at Scopus
  342. J. Y. Zhang, Y. F. Diao, H. R. Kim, and D. I. Jin, “Inhibition of endoplasmic reticulum stress improves mouse embryo development,” PLoS ONE, vol. 7, Article ID e40433, 2012. View at Google Scholar
  343. Q. Zhu, J. J. Zhong, J. F. Jin et al., “Tauroursodeoxycholate, a chemical chaperone, prevents palmitate-induced apoptosis in pancreatic beta-cells by reducing ER stress,” Experimental and Clinical Endocrinology & Diabetes. In press.
  344. Z. Zhang, N. Tong, Y. Gong et al., “Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis after ischemia-reperfusion injury,” Neuroscience Letters, vol. 504, pp. 88–92, 2011. View at Google Scholar
  345. C. Penas, E. Verdú, E. Asensio-Pinilla et al., “Valproate reduces CHOP levels and preserves oligodendrocytes and axons after spinal cord injury,” Neuroscience, vol. 178, pp. 33–44, 2011. View at Publisher · View at Google Scholar · View at Scopus
  346. C. D. Bown, J. F. Wang, B. Chen, and L. T. Young, “Regulation of ER stress proteins by valproate: therapeutic implications,” Bipolar Disorders, vol. 4, no. 2, pp. 145–151, 2002. View at Publisher · View at Google Scholar · View at Scopus
  347. T. Hiroi, H. Wei, C. Hough, P. Leeds, and D. M. Chuang, “Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2,” Pharmacogenomics Journal, vol. 5, no. 2, pp. 102–111, 2005. View at Publisher · View at Google Scholar · View at Scopus
  348. L. Shao, X. Sun, L. Xu, L. T. Young, and J. F. Wang, “Mood stabilizing drug lithium increases expression of endoplasmic reticulum stress proteins in primary cultured rat cerebral cortical cells,” Life Sciences, vol. 78, no. 12, pp. 1317–1323, 2006. View at Publisher · View at Google Scholar · View at Scopus
  349. Y. Inokuchi, Y. Nakajima, M. Shimazawa et al., “Effect of an inducer of BiP, a molecular chaperone, on endoplasmic reticulum (ER) stress-induced retinal cell death,” Investigative Ophthalmology and Visual Science, vol. 50, no. 1, pp. 334–344, 2009. View at Publisher · View at Google Scholar · View at Scopus
  350. T. Kudo, S. Kanemoto, H. Hara et al., “A molecular chaperone inducer protects neurons from ER stress,” Cell Death and Differentiation, vol. 15, no. 2, pp. 364–375, 2008. View at Publisher · View at Google Scholar · View at Scopus
  351. M. Boyce, K. F. Bryant, C. Jousse et al., “A selective inhibitor of elF2α dephosphorylation protects cells from ER stress,” Science, vol. 307, no. 5711, pp. 935–939, 2005. View at Publisher · View at Google Scholar · View at Scopus
  352. M. J. Fullwood, W. Zhou, and S. Shenolikar, “Targeting phosphorylation of eukaryotic initiation factor-2alpha to treat human disease,” Progress in Molecular Biology and Translational Science, vol. 106, pp. 75–106, 2012. View at Google Scholar
  353. P. Tsaytler, H. P. Harding, D. Ron, and A. Bertolotti, “Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis,” Science, vol. 332, no. 6025, pp. 91–94, 2011. View at Publisher · View at Google Scholar · View at Scopus
  354. V. Appierto, P. Tiberio, M. G. Villani, E. Cavadini, and F. Formelli, “PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation,” Carcinogenesis, vol. 30, no. 5, pp. 824–831, 2009. View at Publisher · View at Google Scholar · View at Scopus
  355. J. H. Choi, A. Y. Choi, H. Yoon et al., “Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen species production and CHOP induction,” Experimental and Molecular Medicine, vol. 42, no. 12, pp. 811–822, 2010. View at Publisher · View at Google Scholar · View at Scopus
  356. J. D. Malhotra, H. Miao, K. Zhang et al., “Antioxidants reduce endoplasmic reticulum stress and improve protein secretion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 47, pp. 18525–18530, 2008. View at Publisher · View at Google Scholar · View at Scopus
  357. S. Takizawa, Y. Izuhara, Y. Kitao et al., “A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia,” Brain Research, vol. 1183, no. 1, pp. 124–137, 2007. View at Publisher · View at Google Scholar · View at Scopus
  358. T. Satoh, S. I. Okamoto, J. Cui et al., “Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 3, pp. 768–773, 2006. View at Publisher · View at Google Scholar · View at Scopus
  359. A. D. Kraft, D. A. Johnson, and J. A. Johnson, “Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult,” Journal of Neuroscience, vol. 24, no. 5, pp. 1101–1112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  360. A. Y. Shih, P. Li, and T. H. Murphy, “A small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo,” Journal of Neuroscience, vol. 25, no. 44, pp. 10321–10335, 2005. View at Publisher · View at Google Scholar · View at Scopus
  361. A. T. Dinkova-Kostova, K. T. Liby, K. K. Stephenson et al., “Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 12, pp. 4584–4589, 2005. View at Publisher · View at Google Scholar · View at Scopus
  362. E. L. O. A, J. Han, M. Ben Abdrabbah, and H. Isoda, “Down regulation effect of Rosmarinus officinalis polyphenols on cellular stress proteins in rat pheochromocytoma PC12 cells,” Cytotechnology, vol. 64, pp. 231–240, 2012. View at Google Scholar
  363. T. Satoh, T. Rezaie, M. Seki et al., “Dual neuroprotective pathways of a proelectrophilic compound via HSF-1-activated heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes,” Journal of Neurochemistry, vol. 119, pp. 569–578, 2011. View at Google Scholar
  364. X. Wang and D. Ron, “Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase,” Science, vol. 272, no. 5266, pp. 1347–1349, 1996. View at Google Scholar · View at Scopus
  365. S. Tajiri, S. Oyadomari, S. Yano et al., “Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP,” Cell Death and Differentiation, vol. 11, no. 4, pp. 403–415, 2004. View at Publisher · View at Google Scholar · View at Scopus
  366. H. Zhu, S. Xiao, H. Sun et al., “Activation and crosstalk between the endoplasmic reticulum road and JNK pathway in ischemia-reperfusion brain injury,” Acta Neurochirurgica, vol. 154, pp. 1197–1203, 2012. View at Google Scholar
  367. G. B. Park, Y. S. Kim, H. K. Lee et al., “Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway,” Journal of Immunology, vol. 185, no. 12, pp. 7274–7284, 2010. View at Publisher · View at Google Scholar · View at Scopus
  368. S. B. Christensen, D. Mondrup Skytte, S. R. Denmeade et al., “A trojan horse in drug development: targeting of thapsigargins towards prostate cancer cells,” Anti-Cancer Agents in Medicinal Chemistry, vol. 9, no. 3, pp. 276–294, 2009. View at Google Scholar · View at Scopus
  369. A. H. Schönthal, “Antitumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy,” Neurosurgical Focus, vol. 20, no. 4, p. E21, 2006. View at Publisher · View at Google Scholar · View at Scopus
  370. D. N. Criddle, J. V. Gerasimenko, H. K. Baumgartner et al., “Calcium signalling and pancreatic cell death: apoptosis or necrosis?” Cell Death and Differentiation, vol. 14, no. 7, pp. 1285–1294, 2007. View at Publisher · View at Google Scholar · View at Scopus
  371. A. Görlach, P. Klappa, and T. Kietzmann, “The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control,” Antioxidants and Redox Signaling, vol. 8, no. 9-10, pp. 1391–1418, 2006. View at Publisher · View at Google Scholar · View at Scopus
  372. A. Banerjee, J. Y. Lang, M. C. Hung et al., “Unfolded protein response is required in nu/nu mice microvasculature for treating breast tumor with tunicamycin,” Journal of Biological Chemistry, vol. 286, pp. 29127–29138, 2011. View at Google Scholar
  373. A. D. Elbein, “The tunicamycins—useful tools for studies on glycoproteins,” Trends in Biochemical Sciences, vol. 6, pp. 219–221, 1981. View at Google Scholar · View at Scopus
  374. L. Andresen, S. L. Skovbakke, G. Persson et al., “2-deoxy D-glucose prevents cell surface expression of NKG2D ligands through inhibition of N-linked glycosylation,” The Journal of Immunology, vol. 188, pp. 1847–1855, 2012. View at Google Scholar
  375. S. Kishi, K. Shimoke, Y. Nakatani et al., “Nerve growth factor attenuates 2-deoxy-d-glucose-triggered endoplasmic reticulum stress-mediated apoptosis via enhanced expression of GRP78,” Neuroscience Research, vol. 66, no. 1, pp. 14–21, 2010. View at Publisher · View at Google Scholar · View at Scopus
  376. M. Csala, É. Margittai, and G. Bánhegyi, “Redox control of endoplasmic reticulum function,” Antioxidants and Redox Signaling, vol. 13, no. 1, pp. 77–108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  377. G. Bánhegyi, J. Mandl, and M. Csala, “Redox-based endoplasmic reticulum dysfunction in neurological diseases,” Journal of Neurochemistry, vol. 107, no. 1, pp. 20–34, 2008. View at Publisher · View at Google Scholar · View at Scopus
  378. M. Gorska, U. Popowska, A. Sielicka-Dudzin et al., “Geldanamycin and its derivatives as Hsp90 inhibitors,” Frontiers in Bioscience, vol. 17, pp. 2269–2277, 2012. View at Google Scholar
  379. B. Lawson, J. W. Brewer, and L. M. Hendershot, “Geldanamycin, an hsp90/GRP94-binding drug, induces increased transcription of endoplasmic reticulum (ER) chaperones via the ER stress pathway,” Journal of Cellular Physiology, vol. 174, pp. 170–178, 1998. View at Google Scholar
  380. J. S. Carew, S. T. Nawrocki, Y. V. Krupnik et al., “Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL,” Blood, vol. 107, no. 1, pp. 222–231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  381. J. E. Casanova, “Regulation of Arf activation: the Sec7 family of guanine nucleotide exchange factors,” Traffic, vol. 8, no. 11, pp. 1476–1485, 2007. View at Publisher · View at Google Scholar · View at Scopus
  382. D. R. Fels, J. Ye, A. T. Segan et al., “Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathways,” Cancer Research, vol. 68, no. 22, pp. 9323–9330, 2008. View at Publisher · View at Google Scholar · View at Scopus
  383. J. J. Gills, J. Lopiccolo, and P. A. Dennis, “Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy,” Autophagy, vol. 4, no. 1, pp. 107–109, 2008. View at Google Scholar · View at Scopus
  384. S. T. Nawrocki, J. S. Carew, K. Dunner Jr. et al., “Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells,” Cancer Research, vol. 65, no. 24, pp. 11510–11519, 2005. View at Publisher · View at Google Scholar · View at Scopus