Journal of Gynecologic Oncology

Korean Society of Gynecologic Oncology (대한부인종양학회)
권호 표지

Effects of cell growth inhibition on the combination of cisplatin with green tea extracts

시스플라틴과 녹차 추출물의 병용에 의한 세포성장 저해 효과

Kim, Hyun-Kyung;Kang, Young-Haw;Kwak, Sun-Young;Ding, Guo-Hua;Bae, Su-Mi;Park, Eun-Kyung;Lee, Yong-Seok;Kim, Jung;Kim, Yong-Wook;Ro, Duck-Yeong;Lee, Joon-Mo;Namkoong, Sung-Eun;Chang, Hong-Seok;Chun, Heung-Jae;Lim, Dae-Seog;Ahn, Woong-Shick
김현경;강영화;곽선영;정국화;배수미;박은경;이용석;김정;김용욱;노덕영;이준모;남궁성은;장홍석;전흥재;임대석;안웅식

  • Published : 2005.12.20
⟨ Previous Next ⟩

Abstract

Objective: The chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum (II)) is particularly effective against cervical cancer. The purpose of this study is to elucidate combination effect of cisplatin and green tea extracts on the growth inhibition of TC-1 cell. Methods: To observe the anti-proliferative effects, we treated different doses of cisplatin (0.1, 0.5, 2.5 uM), GTP (1, 5, 25 ug/ml) and EGCG (25, 50, 100 uM). to TC-1 cells. Also, we treated 0.5 uM of cisplatin and different doses of GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM). Cell viability was scored by use of MTT assay. In addition, E6 gene expression patterns in TC-1 cell were investigated by using RT-PCR. Results: Cell growth inhibition in a dose dependent was observed at the different concentration of ciaplatin, GTP and EGCG. Also, in the groups treated by 0.5 uM of cisplatin and GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM), the inhibition of cell growth showed with 12.2%, 6.9% and 63.4%, 72.2% as compared to the group treated by cisplatin only. In RT-PCR, down regulation of E6 was shown. Conclusion: Additive effect of the combination of cisplatin with GTP or EGCG on the inhibition of cell growth was observed. This effect suggests the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

목적: 시스플라틴은 자궁경부암 치료에 사용되는 효과적인 항암제이다. 본 연구에서는 인유두종바이러스(human papillomavirus; HPV) E6/E7 유전자를 발현하는 TC-1 세포주에서 시스플라틴과 함께 녹차추출물을 병용하여 상승되는 세포성장 억제효과를 살펴보고자 하였다. 연구 방법: TC-1 세포주를 배양하여 시스플라틴과 녹차 추물물인 GTP (green tea polyphenol)와 EGCG ((-)-Epigallocatechin gallate)를 각각 혹은 동시에 처리한 후 세포독성에 미치는 영향을 MTT법으로 조사하였다. 인유두종바이러스의 종양 유전자인 E6의 발현 변화는 RT-PCR을 통하여 확인하였다. 결과: 시스플라틴, GTP, EGCG의 농도가 증가함에 따라 세포 성장억제 비율이 증가됨을 확인하였다. 또한 시스플라틴 0.5 uM과 1 또는 5 ug/ml의 GTP 혹은 25 또는 50 uM의 EGCG를 동시에 처리한 경우 시스플라틴 단독 처리군에 비해 각각 12.2%와 6.9% 그리고 63.4%와 72.2%의 세포성장 억제효과가 나타났다(p＜0.05). 또한 인유두종바이러스의 종양 유전자인 E6의 발현이 현저히 억제됨을 확인하였다. 결론: TC-1 세포주에서 시스플라틴과 GTP 혹은 EGCG의 병용한 경우 단독 처리군에 비해 세포성장 억제효과가 상승되고 인유두종바이러스의 종양 유전자인 E6의 발현이 저해됨을 확인할 수 있었다. 따라서 단독으로 사용 할 때보다 적은 용량의 시스플라틴으로도 항암효과를 기대할 수 있으므로 약물내성 및 신 독성 등의 부작용을 줄일 수 있을 것으로 생각된다.

Keywords

References

  1. Crown JP. The platinum agents: a role in breast cancer treatment? Semin Oncol 2001; 28: 28-37
  2. Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci 2000; 57: 1229-35 https://doi.org/10.1007/PL00000762
  3. Kartalou M, Essigmann JM. Mechanisms of resistance to cisplatin. Mutat Res 2001; 478: 23-43 https://doi.org/10.1016/S0027-5107(01)00141-5
  4. Albets DS, Garcia D, Mason-Liddil N. Cisplatin in advanced cancer of the cervix: an update Semin Oncol 1991; 18: 11-24
  5. Wang G, Reed E, Li QQ. Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer. Oncol Rep 2004; 12: 955-65
  6. Sardi JE. Neoadjuvant chemotheraphy in gynecologic oncology. Surg Clin North Am 2001; 81: 965-85 https://doi.org/10.1016/S0039-6109(05)70176-6
  7. McAfee SL, Seiden MV. High dose chemotherapeutic strategies in the treatment of epithelial ovarian carcinoma. Curr Opin Obstet Gynecol 1999; 11: 17-21 https://doi.org/10.1097/00001703-199901000-00004
  8. Yoshida Y, Hosokawa K, Dantes A, Tajima K, Kotsuji F, Amsterdam A. Theophlline and cisplatin synergize in down regulation of BCL-2 induction of apoptosis in human granulosa cells transformed by a mutated p53 (p53 val135) and Ha-ras oncogene. Int J Oncol 2000; 17: 227-35
  9. Tsao AS, Kim ES, Hong WK. Chemoprevention of cancer CA cancer. J Cin 2004; 54: 150-80
  10. Follen M, Meyskens FL Jr, Alvarez RD, Walker JL, Bell MC, Storthz KA, et al. Cervical cancer chemoprevention, vaccines and surrogate endpoint biomarkers. Cancer 2003; 98: 2044-51 https://doi.org/10.1002/cncr.11674
  11. Ahn WS, Huh SW, Bae SM, Lee IP, Lee JM, Namkoong SE, et al. A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, Caski cells, through apoptosis, G (1) arrest and regulation of gene expression. DNA Cell Biol 2003; 22: 217-24 https://doi.org/10.1089/104454903321655846
  12. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changeing the glutathion level. Cancer Let 2004; 212: 177-84 https://doi.org/10.1016/j.canlet.2004.03.040
  13. Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ. Scavenging effect of green tea and natural antioxidants on active oxygen radicals. Biochem Mol Biol Int 1989; 14: 175-85
  14. Martinez J, Moreno JJ. Effects of resverattrol, a natural polyphenollic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol 2000; 59: 865-70 https://doi.org/10.1016/S0006-2952(99)00380-9
  15. Cloutier MM, Guernsey L. Tannin inhibition of protein kinase C in airway epithelium. Lung 1995; 173: 307-19
  16. Iwai K, Onodera A, Mastsue H. Antioxidant activity and inhibitory effect of Gamazumi (Viburnum dilatatum THUMB.) on oxidative damage induced by water immersion restraint stress in rats. Int J Food Sci Natr 2001; 52: 443-51 https://doi.org/10.1080/09637480120078339
  17. Huh SW, Bae SM, Kim YW, Lee JM, Namkoong SE, Lee IP, et al. Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines. Gynecol Oncol 2004; 94: 760-8 https://doi.org/10.1016/j.ygyno.2004.05.031
  18. Sah JF, Balasubramanian S, Eckert RL, Rorke EA. Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases. J Biol Chem 2004; 279: 12755-62 https://doi.org/10.1074/jbc.M312333200
  19. Park OJ, Surh YJ. Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. Toxicol Lett 2004; 150: 43-56 https://doi.org/10.1016/j.toxlet.2003.06.001
  20. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22: 7265-79 https://doi.org/10.1038/sj.onc.1206933