YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Anticancer Effects of the Isoflavone Extract from Chungkukjang via Cell Cycle Arrest and Apoptosis in MDA-MB-453 Cells

청국장에서 얻은 Isoflavone의 MDA-MB-453세포에서 항암효과 및 관련 기전

  • Shin, Jin Young (College of Pharmacy, Sookmyung Women's University) ;
  • Kim, Taehee (College of Pharmacy, Sookmyung Women's University) ;
  • Kim, An Keun (College of Pharmacy, Sookmyung Women's University)
  • 신진영 (숙명여자대학교 약학대학) ;
  • 김태희 (숙명여자대학교 약학대학) ;
  • 김안근 (숙명여자대학교 약학대학)
  • Received : 2014.02.05
  • Accepted : 2014.02.24
  • Published : 2014.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

The objective of this study is to evaluate the anticancer effects of the isoflavone extract from Chungkukjang in human breast cancer, MDA-MB-453 cells. For this study, MDA-MB-453 cells were treated with 12.5, 25, and $50{\mu}g$ isoflavone extract for 24, 48, and 72 hr. Cell proliferations were decreased in a time- and dose-dependent manner. Reduced cell proliferation was suspected by apoptosis or cell cycle arrest. Therefore, after treatment of $50{\mu}g$ isoflavone extract, apoptotic cells were investigated by annexin V staining. The results indicated that isoflavone extract increased the number of early apoptotic cells compared with control. Cleaved PARP was also increased. Next, we investigated the cell cycle and related proteins. The isoflavone extract leads to cell cycle arrest at the G2/M phase. Moreover isoflavone extract had influenced cell cycle relate proteins such as cyclin B1, cyclin A, and p21. These results suggest that isoflavone extract from Chungkukjang induce apoptosis and cell cycle arrest at G2/M phase via regulation of cell cycle-related proteins in MDA-MB-453 cells.

Keywords

References

  1. Wada, K., Nakamura, K., Tamai, Y., Tsuji, M., Kawachi, T., Hori, A., Takeyama, N., Tanabashi, S., Matsushita, S., Tokimitsu, N. and Nagata, C. : Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study. Int. J. Cancer 13, 952 (2013).
  2. Nagata, C. : Factors to consider in the association between soy isoflavone intake and breast cancer risk. J. Epidemiol. 20, 83 (2010). https://doi.org/10.2188/jea.JE20090181
  3. Messina, M. J., Persky, V., Setchell, K. D. and Barnes, S. : Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer 21, 133 (1994). https://doi.org/10.1080/01635589409514311
  4. Kao, T. H., Wu, W. M., Hung, C. F., Wu, W. B. and Chen, B. H. : Anti-inflammatory effects of isoflavone powder produced from soybean cake. J. Agric. Food Chem. 55, 11068 (2007). https://doi.org/10.1021/jf071851u
  5. Messina, M. and Messina, V. : Increasing use of soyfoods and their potential role in cancer prevention. J. Am. Diet Assoc. 91, 836 (1991).
  6. Molteni, A., Brizio-Molteni, L. and Persky, V. : In vitro hormonal effects of soybean isoflavones. J. Nutr. 125, 751S (1995).
  7. Kennedy, A. R. : The evidence for soybean products as cancer preventive agents. J. Nutr. 125, 733S (1995).
  8. Knight, D. C. and Eden, J. A. : A review of the clinical effects of phytoestrogens. Obstet. Gynecol. 87, 897 (1996).
  9. Kurzer, M. S. and Xu, X. : Dietary phytoestrogens. Annu. Rev. Nutr. 17, 353 (1997). https://doi.org/10.1146/annurev.nutr.17.1.353
  10. Kim, N. Y., Song, E. J., Kwon, D. Y., Kim, H. P. and Heo, M. Y. : Antioxidant and antigenotoxic activities of Korean fermented soybean. Food Chem. Toxicol. 46, 1184 (2008). https://doi.org/10.1016/j.fct.2007.12.003
  11. Lewis, C. : A review of the use of chemoprotectants in cancer chemotherapy. Drug Saf. 11, 153 (1994). https://doi.org/10.2165/00002018-199411030-00002
  12. Hickman, J. A. : Apoptosis induced by anticancer drugs. Cancer Metastasis Rev. 11, 121 (1992). https://doi.org/10.1007/BF00048059
  13. El-Kenawi, A. E. and El-Remessy, A. B. : Angiogenesis inhibitors in cancer therapy: mechanistic perspective on classification and treatment rationales. Br. J. Pharmacol. 170, 712 (2013). https://doi.org/10.1111/bph.12344
  14. Qu, Z., MacLellan, W. R. and Weiss, J. N. : Dynamics of the cell cycle: checkpoints, sizers, and timers. Biophys. J. 85, 3600 (2003). https://doi.org/10.1016/S0006-3495(03)74778-X
  15. Pines, J. : Cyclins and cyclin-dependent kinases: a biochemical view. Biochem. J. 308, 697 (1995). https://doi.org/10.1042/bj3080697
  16. Hickman, J. A. : Apoptosis induced by anticancer drugs. Cancer Metastasis Rev. 11, 121 (1992). https://doi.org/10.1007/BF00048059
  17. Jin, S., Zhang, Q. Y., Kang, X. M., Wang, J. X. and Zhao, W. H. : Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann. Oncol. 21, 263 (2010). https://doi.org/10.1093/annonc/mdp499
  18. Choi, E. J. and Kim, G. H. : Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells. Phytomedicine 15, 683 (2008). https://doi.org/10.1016/j.phymed.2008.04.006
  19. Sergeev, I. N. : Genistein induces Ca2+ -mediated, calpain/ caspase-12-dependent apoptosis in breast cancer cells. Biochem. Biophys. Res. Commun. 321, 462 (2004). https://doi.org/10.1016/j.bbrc.2004.06.173
  20. Li, Z., Li, J., Mo, B., Hu, C., Liu, H., Qi, H., Wang, X. and Xu, J. : Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway. Toxicol. In Vitro 22, 1749 (2008). https://doi.org/10.1016/j.tiv.2008.08.001
  21. Zheng, J., Jin, Y. and Row, K. H. : Analysis of isoflavones from Korean and Chinese soybean and processed products by HPLC. J. Korean Chem. Society 49, 349 (2005). https://doi.org/10.5012/jkcs.2005.49.4.349
  22. Choi, Y. H., Lim, H., Heo, M. Y., Kwon, D. Y. and Kim, H. P. : Anti-inflammatory activity of the ethanol extract of Chungkukjang, Korean fermented bean: 5-lipoxygenase inhibition. J. Med. Food 11, 539 (2008). https://doi.org/10.1089/jmf.2007.0125
  23. Kim, N. Y., Song, E. J., Kwon, D. Y., Kim, H. P. and Heo, M. Y. : Antioxidant and antigenotoxic activities of Korean fermented soybean. Food Chem. Toxicol. 46, 1184 (2008). https://doi.org/10.1016/j.fct.2007.12.003
  24. Hwang, J. S., Yoo, H. J., Song, H. J., Kim, K. K., Chun, Y. J., Matsui, T. and Kim, H. B. : Inflammation-related signaling pathways implicating TGF$\beta$ are revealed in the expression profiling of MCF7 cell treated with fermented soybean, chungkookjang. Nutr. Cancer 63, 645 (2011). https://doi.org/10.1080/01635581.2011.551987
  25. Onozawa, M., Fukuda, K., Ohtani, M., Akaza, H., Sugimura, T. and Wakabayashi, K. : Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP. Jpn. J. Clin. Oncol. 28, 360 (1998). https://doi.org/10.1093/jjco/28.6.360
  26. Delhalle, S., Duvoix, A., Schnekenburger, M., Morceau, F., Dicato, M. and Diederich, M. : An introduction to the molecular mechanisms of apoptosis. Ann. N. Y. Acad. Sci. 1010, 1 (2003). https://doi.org/10.1196/annals.1299.001
  27. Hong, S. J., Dawson, T. M. and Dawson, V. L. : Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling. Trends Pharmacol. Sci. 25, 259 (2004). https://doi.org/10.1016/j.tips.2004.03.005
  28. Prez-Roger, I., Ivorra, C., Dez, A., Corts, M. J., Poch, E., Sanz- Gonzlez, S. M. and Andrs, V. : Inhibition of cellular proliferation by drug targeting of cyclin-dependent kinases. Curr. Pharm. Biotechnol. 1, 107 (2000). https://doi.org/10.2174/1389201010001010107
  29. O'Connor, P. M. and Kohn, K. W. : A fundamental role for cell cycle regulation in the chemosensitivity of cancer cells? Semin. Cancer Biol. 3, 409 (1992).
  30. Gottesman, M. M. : Report of a meeting: molecular basis of cancer therapy. J. Natl. Cancer Inst. 86, 1277 (1994). https://doi.org/10.1093/jnci/86.17.1277
  31. Zhou, J. R., Mukherjee, P., Gugger, E. T., Tanaka, T., Blackburn, G. L. and Clinton, S. K. : Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis. Cancer Res. 58, 5231 (1998).