YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Efficacy of Saururus chinensis on Cervical Cancer Cells : The Inhibitory Effect on the Function of E6 and E7 Oncogenes of HPV Type 16

삼백초 추출물의 자궁경부암세포 억제 효능

  • Chung, Yeon-Gu (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hae-Sook (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Kyung-Ae (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Joung, Ok (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Won-Keun (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Kwang-Dong (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lim, Jong-Seok (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Moon, Ja-Young (Department of Biochem. and Health Science, Changwon National University) ;
  • Cho, Yong-Kweon (Department of Biochem. and Health Science, Changwon National University) ;
  • Park, Sue-Nie (Department of Viral products, Korea Food and Drug Administration) ;
  • Yoon, Do-Young (Laboratory of cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology)
  • 정연구 (한국생명공학연구원 세포생물학연구실) ;
  • 이해숙 (한국생명공학연구원 세포생물학연구실) ;
  • 이경애 (한국생명공학연구원 세포생물학연구실) ;
  • 정옥 (한국생명공학연구원 세포생물학연구실) ;
  • 오원근 (한국생명공학연구원 세포생물학연구실) ;
  • 김광동 (한국생명공학연구원 세포생물학연구실) ;
  • 임종석 (한국생명공학연구원 세포생물학연구실) ;
  • 문자영 (창원대학교 보건.생화학과) ;
  • 조용권 (창원대학교 보건.생화학과) ;
  • 박순희 (한국식품의약품안전청 바이러스제제과) ;
  • 윤도영 (한국생명공학연구원 세포생물학연구실)
  • Published : 2002.12.01
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Abstract

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV type 16 and 18) and cervical cancer has been well known. An extract of Saururus chinensis, named as PE-46, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. PE-46 inhibited the proliferation of human cervical cancer cell lines in a dose response manner. PE-46 also inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, PE-46 inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by PE-46. SiHa cells treated with PE-46 induced G0/G1 arrest, resulting in inhibition of growth. Our study showed that the PE-46 can inhibit the cervical carcinomas via both inhibition of bindings between oncogenes and tumor suppressors, and inhibition of G1longrightarrowS transition. PE-46 inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus could be used as a putative modulating agent for the treatment of cervical carcinomas caused by HPV.

Keywords

References

  1. 이창복 : 대한식물도감, 향문사, 서울. p.252 (1979)
  2. 김재길 : 원색 천연의탤 대사전(하), 남산당, 서울, p174 (1984)
  3. 新文豊 出判公司 : 新編 中藥大辭典(中), 薹北. p. 174 (1984)
  4. Hsu, H, Y. Chen, Y, P. Shen, S, J. Hsu, C, S. Chen, C, C. and Chang, H, C: Oriental Materia Medica, Oriental healing arts institute, Long Beach, P. 308 (1986)
  5. Sung, S. H., Lee, E. J., Cho, J. H., Kim, H. S and Kim, Y. C. : Sauchinone, a lignan from Saururus chinnensis, attenuates $CCl_4$-induced toxicity in primary cultures of rat hepatocytes. Biol. Pharm. Bull. 23, 666 (2000)
  6. Sung, S. H. and Kim, Y. C. : Hepatoprotective diasteromeric lignans from Saururus chinensis herbs. J Nat. Prod. 63, 1019 (2000) https://doi.org/10.1021/np990499e
  7. Park, S. K., Oh, G, J., Bae, C. I., Kim, H. J., Han, W. S., Chung, S. G. and Cho, E. W. : Studies on the cytotoxic constituent of Saururus chenensis ($L_{OUR}$) $B_{AILL}$. Yakhak Hoeji, 41, 704 (1997)
  8. Park, S. K., Oh, G, J., Kim, H. T., Kim, H. J., Chung, S. G. and Cho, E. H. : Analogesic constituent from the herba of Saururus chenensis ($L_{OUR}$) $B_{AILL}$. Yakhak Hoeji, 42, 238 (1998)
  9. Wie, M. B. : Protective effects of Opuntis ficus-Indica and Saururus chinensis on free radical-induced neuronal injury in mouse cortical cell cultures. Yakhak Hoeji, 44, 613 (2000)
  10. Scheffner, M., Munger, K., Byrne, J.C. and Howley, P. M. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc. Nail. Acad. Sci. 88, 5523 (1991)
  11. Isfort, R. J., Cody, D. B., Lovell, G. and Doersen, C. J. Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. Mol. Carcinog. 14, 170 (1999)
  12. Yang, X., Nakao, Y., Pater, M. M., Tang, S. C. and Pater, A. Expression of cellular genes in HPV16-immortalized and cigarette smoke condensate-transformed human endocervical cells. J. Cell. Biochem. 66: 309 (1977)
  13. Yang, X., Sham, J. S., Ng, M. H., Tsao, S. W., Zhang, D., S. W. L and Cao L. LMP1 of epstein-barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. J. Virol. 74, 883 (2000)
  14. Garbe, J., Wong, M., Wigington, D., Yaswen, P. and Stampfer, M. R. Viral oncogenes accelerate conversion to immortality of cultured conditionally immortal human mammary epithelial cells. Oncogene 18, 2169 (1999)
  15. Henkler, F. F. and Koshy, R. Hepatitis B virus transcriptional activators: mechanisms and possible role in oncogenesis. J. Viral Hepat. 3, 10 (1996)
  16. Shackney, S. E. and Shankey, T. V. Cell cycle models for molecular biology and molecular oncology: exploring new dimensions. Cytometry 35, 97 (1999)
  17. Reddy, K. B., Keshamouni, V. G. and Chen, Y. Q. The level of tyrosine kinase activity regulates the expression of p21/WAF1 in cancer cells. Int. J. Oncol. 15, 301 (1999)
  18. Tommasino, M. and Crawford, L. Human papillomavirus E6 and E7: proteins which deregulate the cell cycle. BioEssays 17, 509 (1995)
  19. Woodworth, C. D., Cheng, S., Simpson, S., Hamacher, L., Chow, L. T., Broker, T. R. and Dipaolo, J. A. Recombinant retroviruses encoding human papillomavirus type 18 E6 and E7 genes stimulate proliferation and delay differentiation of human keratinocytes early after infection. Oncogene 7, 619 (1992)
  20. Dyson, N., Howley, P. M., Munger, K. and Harlow, E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243, 934 (1989)
  21. Marchuk, D., Drumm, M., Saulino, A. and Collins, F. S. Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res. 19(5), 1154 (1990)
  22. Cho, Y. S., Cho, C. W., Joung, O., Lee, K. A., Park, S. K. and Yoon, D. Y. Development of screening systems for drugs against human papillomvirus-associated cervical cancer: based on E6-E6AP binding. Antiviral Res. 47, 199 (2000) https://doi.org/10.1016/S0166-3542(00)00109-1
  23. Cho, Y. S., Cho, C. W., Kang, J. O., Cho, M. J.. Lee, K. A., Shim, J. H., Kwon, D. H., Choe, Y. K., Park, S. N. and Yoon, D. Y. Development of a screening system for drugs against human papillomvirus-associated cervical cancer: based on E7-Rb binding. J. Biochem. Mol. Biol. 34, 80 (2001)
  24. Pei, X. F. The human papillomavirus E6/E7 genes induce discordant changes in the expression of cell growth regulatory proteins. Carcinogenesis 17, 1395 (1996)
  25. Beerheide, W., Bernard, H. D., Tan, Y. J, Ganesan, A., Rice, W. G. and Ting, A. E. Potential drugs against cervical cancer: Zinc-ejecting inhibitors of the human papillomavirus type 16 E6 oncoprotein. J. Natl. Cancer Institute, 91(14), 1211 (1999) https://doi.org/10.1093/jnci/91.14.1211