Synergistic Effect of Cisplatin and Berberine on Inhibition of Cell Growth and Induction of Apoptosis involving Oxidative Stress in HeLa Cells

자궁경부암 세포주에서 활성산소종의 영향애 의한 Apoptosis를 통하여 세포성장을 억제하는 Cisplatin과 Berberine의 상승효과

  • Cho, Hae-Joong (Department of Obstetrics and Gynecology, College of Medicine, Wonkwang University)
  • 조해중 (원광대학교 의과대학 산부인과)
  • Published : 2007.08.25

Abstract

Cisplatin is a chemotherapeutic drug which is widely used for cancer therapy including cervical cancer. The purpose of this study is to elucidate synergistic effect of Cisplatin and Berberine on the apoptosis of HeLa cells and to determine whether oxidants are formed as part of apoptotic process. Apoptotic death of HeLa cells by cisplatin and berberine was confirmed by chromatin condensation of HeLa cells and flow cytometric analysis of intracellular ROS(reactive oxygen species) production. In MTT assay, Cell viability was decreased and enhanced ROS generation in combination of cisplatin and berberine significantly, as compared with cisplatin only. Synergistic effect of Cisplatin and Berberine on the inhibition of cell growth by apoptosis was clearly observed and ROS may play an important role in apoptosis. This effect suggest the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

Keywords

References

  1. 1999-2001 한국인 암 발생 통계. 보건복지부 암 발생 통계집. 2005
  2. Green, D.R., Reed, J.C. Mitochondria and apoptosis. Science, 281: 1309-1312, 1998 https://doi.org/10.1126/science.281.5381.1309
  3. Miyajima, A., Nakashima, J., Yoshioka, K. Role of reactive oxygen species in cis-dichlorodiammineplatium-induced cytotoxicity on bladder cancer cells. Br J Cancer, 76: 206-210, 1997 https://doi.org/10.1038/bjc.1997.363
  4. Amin, A.H., Subbaiah, T.V., Abbasi, K.M. Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol. 15: 1067-1076, 1969 https://doi.org/10.1139/m69-190
  5. Akirhter, M.H., Sab, M., Bhide, N.K. Anti-inflammatory effect of berberine in rats injected locally with cholear toxin. Indian J Med Res, 65: 133-141, 1977
  6. Hwang, J.M., Kuo, H.C., Tseng, T.H., Liu, J.Y. Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells. Arch Toxicol. 28: 1-12, 2005
  7. Kobayashi, Y., Yamashita, Y., Fujii, N., Takaboshi, K., Kawakami, T., Kawamura, M., Mizukami, T., Nakano, H. Inhibitors of DNA topoisomerase I and II from the Coptis Rhizomes. Planta Med. 61: 414-418, 1995 https://doi.org/10.1055/s-2006-958127
  8. 고경희, 김신호, 조해중, 오성환, 김흥곤, 박래길. Involvement of Oxidative Stress in Cisplatin-Induced Apoptosis in HeLa Cells. 대한 산부회지 46(12):2410-2416, 2003
  9. 최정호, 조현, 이선영, 오성환, 김흥곤, 박래길. The Study of the Cytotoxic Mechanism of Cisplatin in HeLa Cells. 대한 산부회지 46(10):1989-1998. 2003
  10. 강경화, 허주엽, 서병선. 난소암세포주에서 Apoptosis를 통하여 세포성장을 억제하는 Theophylline과 Cisplatin의 상승효과. 대한산부회지 47(10):1905-1914, 2004
  11. Wang, D., Lippard, S.J. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 4: 307-320, 2005 https://doi.org/10.1038/nrd1691
  12. 허주엽, 임명철, 서병선. 난소암 세포주에서 Topotecan, Cisplatin, Taxol에 대한 화학민감도의 측정과 p53, bcl-2및 세포고사에 관한 연구. 대한산부회지 46(7):1368-1377, 2003
  13. Kobayashi, Y., Yamashita, Y., Fujii, N. et al, Inhibitors of DNA topoisomerase I and II from the Coptis Rhizomes. Planta Med. 61: 414-418, 1995 https://doi.org/10.1055/s-2006-958127
  14. Marta, C., Daniela, K., Viktor, K., Miriam, P., Jaroslav, T., Ján D. Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium. BMC Complementary and Alternative Medicine 2: 2-6, 2002 https://doi.org/10.1186/1472-6882-2-2
  15. Sona, J., Lubos, C., Marta C., Daniela, K. Effect of berberine on proliferation, cell cycle and apoptosis in Hela and L1210 cells. J. Pharmacy and Pharmacology, 55: 1143-1149, 2003 https://doi.org/10.1211/002235703322277186
  16. Baumgartner, M., Sturlan, S., Roth, E., Wessner, B., Bachleitner Hofmann, T. Enhancement of arsenic trioxide-mediated apoptosis using Docosahexaenoic acid in arsenic trioxide- resistant sold tumor cells. Int. J. Cancer, 112: 707-712, 2004 https://doi.org/10.1002/ijc.20462
  17. Oikawa, S.T., Hiraku, Y., Kawanishi, M., Kawanish, S. Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone- induced apoptosis. Life Science 73: 3277-3288, 2003 https://doi.org/10.1016/j.lfs.2003.06.013
  18. Sauer, H., Wartenberg, M., Hescheler, J. Reactive oxygen species as intracellula messengers during cell growth and differentiation. Cell physiol Biochem. 11(4):173-186, 2001 https://doi.org/10.1159/000047804