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International Journal of Breast Cancer
Volume 2013 (2013), Article ID 101705, 17 pages
http://dx.doi.org/10.1155/2013/101705
Research Article

Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells

College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA

Received 12 September 2012; Revised 20 November 2012; Accepted 29 November 2012

Academic Editor: Heather E. Kleiner-Hancock

Copyright © 2013 Abhita Malaviya and Paul W. Sylvester. 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. A. F. Badawi and M. Z. Badr, “Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma,” International Journal of Oncology, vol. 20, no. 6, pp. 1109–1122, 2002. View at Google Scholar · View at Scopus
  2. A. Krishnan, S. A. Nair, and M. R. Pillai, “Biology of PPARγ in cancer: a critical review on existing lacunae,” Current Molecular Medicine, vol. 7, no. 6, pp. 532–540, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Tachibana, D. Yamasaki, K. Ishimoto, and T. Doi, “The role of PPARs in cancer,” PPAR Research, vol. 2008, Article ID 102737, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. X. Wang, R. C. Southard, and M. W. Kilgore, “The increased expression of peroxisome proliferator-activated receptor-γ1 in human breast cancer is mediated by selective promoter usage,” Cancer Research, vol. 64, no. 16, pp. 5592–5596, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. Y. Zaytseva, N. K. Wallis, R. C. Southard, and M. W. Kilgore, “The PPARγ antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARγ-dependent and -independent mechanisms,” Anticancer Research, vol. 31, no. 3, pp. 813–823, 2011. View at Google Scholar · View at Scopus
  6. Y. Y. Zaytseva, X. Wang, R. C. Southard, N. K. Wallis, and M. W. Kilgore, “Down-regulation of PPARγ1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells,” Molecular Cancer, vol. 7, article 90, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. V. Subbarayan, X. C. Xu, J. Kim et al., “Inverse relationship between 15-lipoxygenase-2 and PPAR-γ gene expression in normal epithelia compared with tumor epithelia,” Neoplasia, vol. 7, no. 3, pp. 280–293, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Saez, J. Rosenfeld, A. Livolsi et al., “PPARγ signaling exacerbates mammary gland tumor development,” Genes and Development, vol. 18, no. 5, pp. 528–540, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. Y. Cui, K. Miyoshi, E. Claudio et al., “Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility,” Journal of Biological Chemistry, vol. 277, no. 20, pp. 17830–17835, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. J. D. Burton, D. M. Goldenberg, and R. D. Blumenthal, “Potential of peroxisome proliferator-activated receptor gamma antagonist compounds as therapeutic agents for a wide range of cancer types,” PPAR Research, vol. 2008, Article ID 494161, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. M. A. Lea, M. Sura, and C. Desbordes, “Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and antagonists,” Anticancer Research, vol. 24, no. 5, pp. 2765–2771, 2004. View at Google Scholar · View at Scopus
  12. H. Gronemeyer, J. Å. Gustafsson, and V. Laudet, “Principles for modulation of the nuclear receptor superfamily,” Nature Reviews Drug Discovery, vol. 3, no. 11, pp. 950–964, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. B. S. McIntyre, K. P. Briski, M. A. Tirmenstein, M. W. Fariss, A. Gapor, and P. W. Sylvester, “Antiproliferative and apoptotic effects of tocopherols and tocotrienols on normal mouse mammary epithelial cells,” Lipids, vol. 35, no. 2, pp. 171–180, 2000. View at Google Scholar · View at Scopus
  14. B. S. Mcintyre, K. P. Briski, A. Gapor, and P. W. Sylvester, “Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells,” Experimental Biology and Medicine, vol. 224, no. 4, pp. 292–301, 2000. View at Google Scholar · View at Scopus
  15. S. Shah and P. W. Sylvester, “Tocotrienol-induced caspase-8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells,” Experimental Biology and Medicine, vol. 229, no. 8, pp. 745–755, 2004. View at Google Scholar · View at Scopus
  16. P. W. Sylvester and S. J. Shah, “Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells,” Frontiers in Bioscience, vol. 10, pp. 699–709, 2005. View at Google Scholar · View at Scopus
  17. G. V. Samant and P. W. Sylvester, “γ-tocotrienol inhibits ErbB3-dependent PI3K/Akt mitogenic signalling in neoplastic mammary epithelial cells,” Cell Proliferation, vol. 39, no. 6, pp. 563–574, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. S. V. Bachawal, V. B. Wali, and P. W. Sylvester, “Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells,” BMC Cancer, vol. 10, article 84, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Toker, “Protein kinases as mediators of phosphoinositide 3-kinase signaling,” Molecular Pharmacology, vol. 57, no. 4, pp. 652–658, 2000. View at Google Scholar · View at Scopus
  20. A. S. Baldwin Jr., “The NF-κB and IκB proteins: new discoveries and insights,” Annual Review of Immunology, vol. 14, pp. 649–683, 1996. View at Publisher · View at Google Scholar
  21. F. Fang, Z. Kang, and C. Wong, “Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors,” Molecular Nutrition and Food Research, vol. 54, no. 3, pp. 345–352, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. S. E. Campbell, B. Rudder, R. B. Phillips et al., “γ-tocotrienol induces growth arrest through a novel pathway with TGFβ2 in prostate cancer,” Free Radical Biology and Medicine, vol. 50, no. 10, pp. 1344–1354, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. U. K. Laemmli, “Cleavage of structural proteins during the assembly of the head of bacteriophage T4,” Nature, vol. 227, no. 5259, pp. 680–685, 1970. View at Publisher · View at Google Scholar · View at Scopus
  24. P. W. Sylvester, H. P. Birkenfeld, H. L. Hosick, and K. P. Briski, “Fatty acid modulation of epidermal growth factor-induced mouse mammary epithelial cell proliferation in vitro,” Experimental Cell Research, vol. 214, no. 1, pp. 145–153, 1994. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Towbin, T. Staehelin, and J. Gordon, “Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications,” Proceedings of the National Academy of Sciences of the United States of America, vol. 76, no. 9, pp. 4350–4354, 1979. View at Google Scholar · View at Scopus
  26. J. B. Kim, H. M. Wright, M. Wright, and B. M. Spiegelman, “ADD1/SREBP1 activates PPARγ through the production of endogenous ligand,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4333–4337, 1998. View at Publisher · View at Google Scholar · View at Scopus
  27. R. J. Tallarida, “Drug synergism: its detection and applications,” Journal of Pharmacology and Experimental Therapeutics, vol. 298, no. 3, pp. 865–872, 2001. View at Google Scholar · View at Scopus
  28. J. D. Burton, M. E. Castillo, D. M. Goldenberg, and R. D. Blumenthal, “Peroxisome proliferator-activated receptor-γ antagonists exhibit potent antiproliferative effects versus many hematopoietic and epithelial cancer cell lines,” Anti-Cancer Drugs, vol. 18, no. 5, pp. 525–534, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Y. Kim, S. S. Kim, and H. G. Cheon, “Differential anti-proliferative actions of peroxisome proliferator-activated receptor-γ agonists in MCF-7 breast cancer cells,” Biochemical Pharmacology, vol. 72, no. 5, pp. 530–540, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. P. W. Sylvester, “Vitamin E and apoptosis,” Vitamins and Hormones, vol. 76, pp. 329–356, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Nesaretnam, N. Guthrie, A. F. Chambers, and K. K. Carroll, “Effect of tocotrienols on the growth of a human breast cancer cell line in culture,” Lipids, vol. 30, no. 12, pp. 1139–1143, 1995. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Nesaretnam, R. Stephen, R. Dils, and P. Darbre, “Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status,” Lipids, vol. 33, no. 5, pp. 461–469, 1998. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Guthrie, A. Gapor, A. F. Chambers, and K. K. Carroll, “Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination,” Journal of Nutrition, vol. 127, no. 3, pp. 544S–548S, 1997. View at Google Scholar · View at Scopus
  34. K. Nesaretnam, S. Dorasamy, and P. D. Darbre, “Tocotrienols inhibit growth of ZR-75-1 breast cancer cells,” International Journal of Food Sciences and Nutrition, vol. 51, pp. S95–S103, 2000. View at Google Scholar · View at Scopus
  35. V. B. Wali, S. V. Bachawal, and P. W. Sylvester, “Combined treatment of γ-tocotrienol with statins induce mammary tumor cell cycle arrest in G1,” Experimental Biology and Medicine, vol. 234, no. 6, pp. 639–650, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. V. B. Wali, S. V. Bachawal, and P. W. Sylvester, “Suppression in mevalonate synthesis mediates antitumor effects of combined statin and γ-tocotrienol treatment,” Lipids, vol. 44, no. 10, pp. 925–934, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. V. B. Wali and P. W. Sylvester, “Synergistic antiproliferative effects of γ-tocotrienol and statin treatment on mammary tumor cells,” Lipids, vol. 42, no. 12, pp. 1113–1123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. S. V. Bachawal, V. B. Wali, and P. W. Sylvester, “Combined γ-tocotrienol and erlotinib/gefitinib treatment suppresses Stat and Akt signaling in murine mammary tumor cells,” Anticancer Research, vol. 30, no. 2, pp. 429–437, 2010. View at Google Scholar · View at Scopus
  39. A. B. Shirode and P. W. Sylvester, “Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling,” Biomedicine and Pharmacotherapy, vol. 64, no. 5, pp. 327–332, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. A. B. Shirode and P. W. Sylvester, “Mechanisms mediating the synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment,” Journal of Bioanalysis and Biomedicine, vol. 3, no. 1, pp. 1–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. N. M. Ayoub, S. V. Bachawal, and P. W. Sylvester, “γ-tocotrienol inhibits HGF-dependent mitogenesis and Met activation in highly malignant mammary tumour cells,” Cell Prolif, vol. 44, pp. 516–526, 2011. View at Publisher · View at Google Scholar
  42. E. Mueller, P. Sarraf, P. Tontonoz et al., “Terminal differentiation of human breast cancer through PPARγ,” Molecular Cell, vol. 1, no. 3, pp. 465–470, 1998. View at Google Scholar · View at Scopus
  43. M. W. Kilgore, P. L. Tate, S. Rai, E. Sengoku, and T. M. Price, “MCF-7 and T47D human breast cancer cells contain a functional peroxisomal response,” Molecular and Cellular Endocrinology, vol. 129, no. 2, pp. 229–235, 1997. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Lee, F. Elwood, J. McNally et al., “T0070907, a selective ligand for peroxisome proliferator-activated receptor γ, functions as an antagonist of biochemical and cellular activities,” Journal of Biological Chemistry, vol. 277, no. 22, pp. 19649–19657, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. L. Michalik, B. Desvergne, and W. Wahli, “Peroxisome-proliferator-activated receptors and cancers: complex stories,” Nature Reviews Cancer, vol. 4, no. 1, pp. 61–70, 2004. View at Google Scholar · View at Scopus
  46. D. Panigrahy, S. Huang, M. W. Kieran, and A. Kaipainen, “PPARγ as a therapeutic target for tumor angiogenesis and metastasis,” Cancer Biology and Therapy, vol. 4, no. 7, pp. 687–693, 2005. View at Google Scholar · View at Scopus
  47. B. Desvergne and W. Wahli, “Peroxisome proliferator-activated receptors: nuclear control of metabolism,” Endocrine Reviews, vol. 20, no. 5, pp. 649–688, 1999. View at Google Scholar · View at Scopus
  48. L. Gelman, G. Zhou, L. Fajas, E. Raspé, J. C. Fruchart, and J. Auwerx, “p300 Interacts with the N- and C-terminal part of PPARγ2 in a ligand- independent and -dependent manner, respectively,” Journal of Biological Chemistry, vol. 274, no. 12, pp. 7681–7688, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. K. A. Burns and J. P. Vanden Heuvel, “Modulation of PPAR activity via phosphorylation,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 952–960, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Goetze, A. Bungenstock, C. Czupalla et al., “Leptin induces endothelial cell migration through Akt, which is inhibited by PPARγ-ligands,” Hypertension, vol. 40, no. 5, pp. 748–754, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Shimada, K. Kojima, K. Yoshiura, H. Hiraishi, and A. Terano, “Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells,” Gut, vol. 50, no. 5, pp. 658–664, 2002. View at Publisher · View at Google Scholar · View at Scopus