Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014 (2014), Article ID 123482, 9 pages
http://dx.doi.org/10.1155/2014/123482
Research Article

Phosphoproteomic Analysis of Gossypol-Induced Apoptosis in Ovarian Cancer Cell Line, HOC1a

1The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
2School of Life Sciences, Tsinghua University, Beijing 100084, China
3Peking University People’s Hospital, Beijing 100044, China
4The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
5Institute of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China

Received 18 May 2014; Revised 18 July 2014; Accepted 20 July 2014; Published 12 August 2014

Academic Editor: Haiteng Deng

Copyright © 2014 Lixu Jin et al. 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. D. Bell, A. Berchuck, M. Birrer et al., “Integrated genomic analyses of ovarian carcinoma,” Nature, vol. 474, no. 7353, pp. 609–615, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. D. S. Miller, J. A. Blessing, C. N. Krasner et al., “Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group,” Journal of Clinical Oncology, vol. 27, no. 16, pp. 2686–2691, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, and M. J. Thun, “Cancer statistics, 2009,” CA: A Cancer Journal for Clinicians, vol. 59, no. 4, pp. 225–249, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. A. A. Ahmed, D. Etemadmoghadam, J. Temple et al., “Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary,” The Journal of Pathology, vol. 221, no. 1, pp. 49–56, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. F. Tas, D. Duranyildiz, H. Oguz, H. Camlica, V. Yasasever, and E. Topuz, “The value of serum bcl-2 levels in advanced epithelial ovarian cancer,” Medical Oncology, vol. 23, no. 2, pp. 213–217, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. N. S. Anderson, L. Turner, S. Livingston, R. Chen, S. V. Nicosia, and P. A. Kruk, “Bcl-2 expression is altered with ovarian tumor progression: an immunohistochemical evaluation,” Journal of Ovarian Research, vol. 2, no. 1, article 16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. A. M. Petros, A. Medek, D. G. Nettesheim et al., “Solution structure of the antiapoptotic protein bcl-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 6, pp. 3012–3017, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Sattler, H. Liang, D. Nettesheim et al., “Structure of Bcl-x(L)-Bak peptide complex: recognition between regulators of apoptosis,” Science, vol. 275, no. 5302, pp. 983–986, 1997. View at Publisher · View at Google Scholar · View at Scopus
  9. A. M. Petros, D. G. Nettesheim, Y. Wang et al., “Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies,” Protein Science, vol. 9, no. 12, pp. 2528–2534, 2000. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Wang, D. Liu, Z. Zhang et al., “Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 13, pp. 7124–7129, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Degterev, A. Lugovskoy, M. Cardone et al., “Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL,” Nature Cell Biology, vol. 3, no. 2, pp. 173–182, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Tzung, K. M. Kim, G. Basãez et al., “Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3,” Nature Cell Biology, vol. 3, no. 2, pp. 183–191, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. G. Wang, Z. Nikolovska-Coleska, C. Yang et al., “Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins,” Journal of Medicinal Chemistry, vol. 49, no. 21, pp. 6139–6142, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. C. L. Oliver, M. B. Miranda, S. Shangary, S. Land, S. Wang, and D. E. Johnson, “(-)-gossypol acts directly on the mitochondria to overcome Bcl-2- and Bcl-XL-mediated apoptosis resistance,” Molecular Cancer Therapeutics, vol. 4, no. 1, pp. 23–31, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. V. Voss, C. Senft, V. Lang et al., “The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma,” Molecular Cancer Research, vol. 8, no. 7, pp. 1002–1016, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Lian, X. Wu, F. He et al., “A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum,” Cell Death and Differentiation, vol. 18, no. 1, pp. 60–71, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Meng, W. Tang, Y. Dai et al., “Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa,” Molecular Cancer Therapeutics, vol. 7, no. 7, pp. 2192–2202, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. R. C. Stein, A. E. A. Joseph, S. A. Matlin, D. C. Cunningham, H. T. Ford, and R. C. Coombes, “A preliminary clinical study of gossypol in advanced human cancer,” Cancer Chemotherapy and Pharmacology, vol. 30, no. 6, pp. 480–482, 1992. View at Google Scholar · View at Scopus
  19. H. Cheong, C. Lu, T. Lindsten, and C. B. Thompson, “Therapeutic targets in cancer cell metabolism and autophagy,” Nature Biotechnology, vol. 30, no. 7, pp. 671–678, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Yu, J. A. Deck, L. A. Hunsaker et al., “Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C41,” Biochemical Pharmacology, vol. 62, no. 1, pp. 81–89, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Le, C. R. Cooper, A. M. Gouw et al., “Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 5, pp. 2037–2042, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Jiang, W. Ye, and Y. C. Lin, “Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFβ/Akt signaling,” International Journal of Molecular Medicine, vol. 24, no. 1, pp. 69–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. S. R. Volate, B. T. Kawasaki, E. M. Hurt et al., “Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells,” Molecular Cancer Therapeutics, vol. 9, no. 2, pp. 461–470, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. S. F. Zerp, R. Stoter, G. Kuipers et al., “AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis,” Radiation Oncology, vol. 4, article 47, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. Z. Hu, J. Sun, X. Zhu, D. Yang, and Y. Zeng, “ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway,” Journal of Translational Medicine, vol. 7, article 74, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Moon, M. Kim, J. Lee, and G. Kim, “Gossypol suppresses NF-κB activity and NF-κB-related gene expression in human leukemia U937 cells,” Cancer Letters, vol. 264, no. 2, pp. 192–200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Ko, S. Shen, L. Yang, C. Lin, and Y. Chen, “Gossypol reduction of tumor growth through ROS-dependent mitochondria pathway in human colorectal carcinoma cells,” International Journal of Cancer, vol. 121, no. 8, pp. 1670–1679, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Sung, J. Ravindran, S. Prasad, M. K. Pandey, and B. B. Aggarwal, “Gossypol induces death receptor-5 through activation of the ROS-ERK-CHOP pathway and sensitizes colon cancer cells to TRAIL,” The Journal of Biological Chemistry, vol. 285, no. 46, pp. 35418–35427, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. M. J. Sikora, J. A. Bauer, M. Verhaegen et al., “Anti-oxidant treatment enhances anti-tumor cytotoxicity of (-)-gossypol,” Cancer Biology and Therapy, vol. 7, no. 5, pp. 769–778, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Cheng, Y. Lo, J. Yeh et al., “Effect of gossypol on intracellular Ca2+ regulation in human hepatoma cells,” Chinese Journal of Physiology, vol. 46, no. 3, pp. 117–122, 2003. View at Google Scholar · View at Scopus
  31. X. Pang, Y. Wu, B. Lu et al., “(-)-Gossypol suppresses the growth of human prostate cancer xenografts via modulating VEGF signaling-mediated angiogenesis,” Molecular Cancer Therapeutics, vol. 10, no. 5, pp. 795–805, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. U. Varol, B. Karaca, D. Tunali et al., “The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: a preliminary molecular framework for gossypol enantiomers,” Experimental Oncology, vol. 31, no. 4, pp. 220–225, 2009. View at Google Scholar · View at Scopus
  33. G. L. Johnson and R. Lapadat, “Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases,” Science, vol. 298, no. 5600, pp. 1911–1912, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Hunter, “Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signaling,” Cell, vol. 80, no. 2, pp. 225–236, 1995. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Tanaka, Y. Terai, A. Tanabe et al., “Prognostic effect of epidermal growth factor receptor gene mutations and the aberrant phosphorylation of Akt and ERK in ovarian cancer,” Cancer Biology and Therapy, vol. 11, no. 1, pp. 50–57, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. D. A. Altomare, Q. W. Hui, K. L. Skele et al., “AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth,” Oncogene, vol. 23, no. 34, pp. 5853–5857, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. Q. Y. Zeng, M. Sun, R. I. Feldman et al., “Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer,” Oncogene, vol. 19, no. 19, pp. 2324–2330, 2000. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Shayesteh, Y. Lu, W. L. Kuo et al., “PlK3CA is implicated as an oncogene in ovarian cancer,” Nature Genetics, vol. 21, no. 1, pp. 99–102, 1999. View at Publisher · View at Google Scholar · View at Scopus
  39. P. K. Kandala and S. K. Srivastava, “Diindolylmethane suppresses ovarian cancer growth and potentiates the effect of cisplatin in tumor mouse model by targeting signal transducer and activator of transcription 3 (STAT3),” BMC Medicine, vol. 10, article 9, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Huang, C. Page, R. K. Reynolds, and J. Lin, “Constitutive activation of Stat 3 oncogene product in human ovarian carcinoma cells,” Gynecologic Oncology, vol. 79, no. 1, pp. 67–73, 2000. View at Publisher · View at Google Scholar · View at Scopus
  41. Z. Duan, R. Foster, D. A. Bell et al., “Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer,” Clinical Cancer Research, vol. 12, no. 17, pp. 5055–5063, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. H. C. Harsha and A. Pandey, “Phosphoproteomics in cancer,” Molecular Oncology, vol. 4, no. 6, pp. 482–495, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Schmelzle and F. M. White, “Phosphoproteomic approaches to elucidate cellular signaling networks,” Current Opinion in Biotechnology, vol. 17, no. 4, pp. 406–414, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. T. E. Thingholm, T. J. D. Jørgensen, O. N. Jensen, and M. R. Larsen, “Highly selective enrichment of phosphorylated peptides using titanium dioxide,” Nature Protocols, vol. 1, no. 4, pp. 1929–1935, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Zhao, L. Li, Q. Lei, and K. Guan, “The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version,” Genes and Development, vol. 24, no. 9, pp. 862–874, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. V. A. Codelia and K. D. Irvine, “Hippo signaling goes long range,” Cell, vol. 150, no. 4, pp. 669–670, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. H. McNeill, M. Sudol, G. Halder, S. Strano, G. Blandino, and Y. Shaul, “The Hippo tumor suppressor pathway: a report on the second workshop on the Hippo tumor suppressor pathway,” Cell Death and Differentiation, vol. 18, no. 8, pp. 1388–1390, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. X. Zhang, J. George, S. Deb et al., “The Hippo pathway transcriptional co-activator, YAP, is an ovarian cancer oncogene,” Oncogene, vol. 30, no. 25, pp. 2810–2822, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. Hao, A. Chun, K. Cheung, B. Rashidi, and X. Yang, “Tumor suppressor LATS1 is a negative regulator of oncogene YAP,” Journal of Biological Chemistry, vol. 283, no. 9, pp. 5496–5509, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. F. Yu, B. Zhao, N. Panupinthu et al., “Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling,” Cell, vol. 150, no. 4, pp. 780–791, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Matsuoka, B. A. Ballif, A. Smogorzewska et al., “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage,” Science, vol. 316, no. 5828, pp. 1160–1166, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Choi, H. Jong, T. Y. Kim et al., “AKAP12/gravin is inactivated by epigenetic mechanism in human gastric carcinoma and shows growth suppressor activity,” Oncogene, vol. 23, no. 42, pp. 7095–7103, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. W. Liu, M. Guan, T. Hu, X. Gu, and Y. Lu, “Re-Expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro,” PLoS ONE, vol. 6, no. 8, Article ID e24015, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Reddy, M. Deguchi, Y. Cheng, and A. J. W. Hsueh, “Actin cytoskeleton regulates hippo signaling,” PLoS ONE, vol. 8, no. 9, 2013. View at Publisher · View at Google Scholar