Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Apicidin Induces Apoptosis via Cytochrome c-Mediated Intrinsic Pathway in Human Ovarian Cancer Cells

  • Ahn, Mee-Young (College of Pharmacy, Pusan National University) ;
  • Na, Yong-Jin (Department of Obstertrics and Gynecology, College of Medicine, Pusan National University) ;
  • Lee, Jae-Won (College of Pharmacy, Pusan National University) ;
  • Lee, Byung-Mu (Division of Toxicology, College of Pharmacy, Sungkyunkwan University) ;
  • Kim, Hyung-Sik (College of Pharmacy, Pusan National University)
  • Published : 2009.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Histone deacetylase (HDAC) inhibitors are a promising class of anticancer agents that inhibit cancer cell growth in vitro and in vivo. Previous report has shown that apicidin inhibited SK-OV-3 cells proliferation and down-regulation of cyclin B1 and CDK1, and up-regulation of $p21^{WAF1}$ and p27. However, the mechanism of apicidin-mediated apoptotic cell death is not clearly understood. For this study, we investigated the mechanism of apoptotic pathway induced by apicidin in human ovarian cancer cell. We found that SK-OV-3 cells treated with apicidin caused an increase in the percentage of cells in the G2/M phase, which preceded apoptosis characterized by the appearance of cells with sub-G1 population. To further investigate the mechanism of apoptosis induction by apicidin, we measured TUNEL assay, poly-ADP ribose polymerase (PARP) cleavage, and caspase activity in SK-OV-3 cells treated with apicidin for 48 h. Apicidin significantly enhanced apoptosis as measured by TUNEL positive apoptotic cells, PARP cleavage, and increased Bax/Bcl-2 ratio. Induction of apoptosis was confirmed by the release of cytochrome c to cytosol. Our data suggest that apicidin-induced apoptosis in SK-OV-3 cells was accompanied by caspase-3 activation and the increase in Bax/Bcl-2 ratio. These data suggest that apicidin may be effective in the treatment of ovarian cancer through activation of intrinsic apoptotic pathway.

Keywords

References

  1. Ahn, M. Y., Jung, J. H., Na, Y. J. and Kim, H. S. (2008). A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells. Gynecol. Oncol. 108, 27-33 https://doi.org/10.1016/j.ygyno.2007.08.098
  2. American Cancer Society. Retrieved September 4, 2007, www.cancer.org
  3. Baradari, V., Huether, A., Hopfner, M., Schuppan, D. and Scherübl, H. (2006). Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells. Endocr. Relat. Cancer 13, 1237-1250 https://doi.org/10.1677/erc.1.01249
  4. Bokelmann, I. and Mahlknecht, U. (2008). Valproic acid sensitizes chronic lymphocytic leukemia cells to apoptosis and restores the balance between pro- and antiapoptotic proteins. Mol. Med. 14, 20-27
  5. Cheong, J. W., Chong, S. Y., Kim, J. Y., Eom, J. I., Jeung, H. K., Maeng, H. Y., Lee, S. T. and Min, Y. H. (2003). Induction of apoptosis by apicidin, a histone deacetylase inhibitor, via the activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive leukemia cells. Clin. Cancer Res. 9, 5018-5027
  6. Ding, Z., Yang, X., Pater, A. and Tang, S. C. (2000). Resistance to apoptosis is correlated with the reduced caspase-3 activation and enhanced expression of antiapoptotic proteins in human cervical multidrug-resistant cells. Biochem. Biophys. Res. Commun. 270, 415-420 https://doi.org/10.1006/bbrc.2000.2432
  7. Eastman, A. (2004). Cell cycle checkpoints and their impact on anticancer therapeutic strategies. J. Cell Biochem. 91, 223-231 https://doi.org/10.1002/jcb.10699
  8. Green, D. R. and Reed, J. C. (1998). Mitochondria and apoptosis. Science 281, 1309-1312 https://doi.org/10.1126/science.281.5381.1309
  9. Han, J. W., Ahn, S. H., Park, S. H., Wang, S. Y., Bae, G. U., Seo, D. W., Kwon, H. K., Hong, S., Lee, H. Y., Lee, Y. W. and Lee, H. W. (2000). Apicidin, a Histone Deacetylase Inhibitor, Inhibits Proliferation of Tumor Cells via Induction of p21WAF1/Cip1 and Gelsolin. Cancer Res. 60, 6068-6074
  10. Im, J. Y., Park, H., Kang, K. W., Choi, W. S. and Kim, H. S. (2008). Modulation of cell cycles and apoptosis by apicidin in estrogen receptor (ER)-positive and-negative human breast cancer cells. Chem. Biol. Interact. 172, 235-244 https://doi.org/10.1016/j.cbi.2008.01.007
  11. Kim, M. S., Son, M. W., Kim, W. B., Park, Y. I. and Moon, A. (2000). Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype. Cancer Lett. 157, 23-30 https://doi.org/10.1016/S0304-3835(00)00465-1
  12. Kim, T. Y., Bang, Y. J. and Robertson, K. D. (2006). Histone deacetylase inhibitors for cancer therapy. Epigenetics 1, 14-23 https://doi.org/10.4161/epi.1.1.2644
  13. Kwon, S. H., Ahn, S. H., Kim, Y. K., Bae, G. U., Yoon, J. W., Hong, S., Lee, H. Y., Lee, Y. W., Lee, H. W. and Han, J. W. (2002). Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J. Biol. Chem. 277, 2073-2080 https://doi.org/10.1074/jbc.M106699200
  14. Liu, T., Kuljaca, S., Tee, A. and Marshall, G. M. (2006). Histone deacetylase inhibitors: Multi-functional anticancer agents. Cancer Treat. Rev. 32, 157-165 https://doi.org/10.1016/j.ctrv.2005.12.006
  15. Marks, P. A., Richon, V. M., Miller, T. and Kelly, W. K. (2004). Histone deacetylase inhibitors. Adv. Cancer Res. 91, 137-168 https://doi.org/10.1016/S0065-230X(04)91004-4
  16. Mogal, A. and Abdulkadir, S. A. (2006). Effects of Histone Deacetylase Inhibitor (HDACi); Trichostatin-A (TSA) on the expression of housekeeping genes. Mol. Cell. Probes 20, 81-86 https://doi.org/10.1016/j.mcp.2005.09.008
  17. Naora, H. and Montell, D. J. (2005). Ovarian cancer metastasis: integrating insights from disparate model organisms. J. Nat. Rev. Cancer 5, 355-366 https://doi.org/10.1038/nrc1611
  18. Petrella, A., D'Acunto, C. W., Rodriquez, M., Festa, M., Tosco, A., Bruno, I., Terracciano, S., Taddei, M., Paloma, L. G. and Parente, L. (2008). Effects of FR235222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukaemia cell lines: role of annexin A1. Eur. J. Cancer 44, 740-749 https://doi.org/10.1016/j.ejca.2008.01.023
  19. Schepper, S. D., Bruwiere, H. L. N., Verhulst, T., Steller, U., Andries, L., Woutesrs, W., Janicot, M., Artis, J., Heusden, J. V. (2003). Inhibition of histone deacetylases by chlamydocin induces apoptosis and proteasome-mediated degradation of surviving. J. Pharm. Exp. Therap. 304, 881-888 https://doi.org/10.1124/jpet.102.042903
  20. Shankar, S. and Srivastava, R. K. (2008). Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis. Adv. Exp. Med. Biol. 615, 261-298 https://doi.org/10.1007/978-1-4020-6554-5_13
  21. Shao, Y., Gao, Z., Marks, P. A. and Jiang, X. (2004). Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc. Natl. Acad. Sci. U.S.A. 101, 18030-18035 https://doi.org/10.1073/pnas.0408345102
  22. Sobola, H. D., Noymana, E. C., Kazanova, D., Figerb, A., Birkenfelda, S., Shapiroa, L. M., Benamouzig, R. and Arber, N. (2006). Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner. Eur. J. Cancer 42, 422-426 https://doi.org/10.1016/j.ejca.2005.11.009
  23. Takai, N., Desmond, J. C., Kumagai, T., Gui, D., Said, J. W., Whittaker, S., Miyakawa, I. and Koeffler, H. P. (2004). Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin. Cancer Res. 10, 1141-1149 https://doi.org/10.1158/1078-0432.CCR-03-0100
  24. Takai, N. and Narahara, H. (2007). Human endometrial and ovarian cancer cells: histone deacetylase inhibitors exhibit antiproliferative activity, potently induce cell cycle arrest, and stimulate apoptosis. Curr. Med. Chem. 14, 2548-2553 https://doi.org/10.2174/092986707782023299
  25. Toh, Y., Yamamoto, M., Endo, K., Ikeda, Y., Baba, H., Kohnoe, S., Yonemasu, H., Hachitanda, Y., Okamura, T. and Sugimachi, K. (2003). Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma. Oncol. Rep. 10, 333-338
  26. Ueda, T., Takai, N., Nishida, M., Nasu, K. and Narahara, H. (2007). Apicidin, a novel histone deacetylase inhibitor, has profound anti-growth activity in human endometrial and ovarian cancer cells. Int. J. Mol. Med. 19, 301-308
  27. Wang, X. (2001). The expanding role of mitochondria in apoptosis. Genes Dev. 15, 2922-2933
  28. Xu, W. S., Parmigiani, R. B., Marks, P. A. (2007). Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26, 5541-5552 https://doi.org/10.1038/sj.onc.1210620

Cited by

  1. Apicidin, a histone deaceylase inhibitor, induces both apoptosis and autophagy in human oral squamous carcinoma cells vol.47, pp.11, 2011, https://doi.org/10.1016/j.oraloncology.2011.07.027
  2. Toxicological evaluation of an apicidin derivative, histone deacetylase inhibitor SD-2007 in mice vol.32, pp.5, 2009, https://doi.org/10.1007/s12272-009-1519-0
  3. Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing vol.325, pp.2, 2012, https://doi.org/10.1016/j.canlet.2012.06.017
  4. Characterization of Tunicamycin as Anti-obesity Agent vol.17, pp.2, 2009, https://doi.org/10.4062/biomolther.2009.17.2.162
  5. Ochnaflavone, a Natural Biflavonoid, Induces Cell Cycle Arrest and Apoptosis in HCT-15 Human Colon Cancer Cells vol.17, pp.3, 2009, https://doi.org/10.4062/biomolther.2009.17.3.282
  6. Dipterocarpus tuberculatus ethanol extract strongly suppresses in vitro macrophage-mediated inflammatory responses and in vivo acute gastritis vol.146, pp.3, 2013, https://doi.org/10.1016/j.jep.2013.01.033
  7. Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells vol.33, pp.4, 2015, https://doi.org/10.3892/or.2015.3776