어성초 추출물의 ICR생쥐와 L1210 세포에 대한 항암작용 및 SOD, GPx 효소활성변화

Anticancer Effect of Houttuynia cordata Extract on Cancered ICR Mouse and L1210 Cells With Changes of SOD and GPx Activities

  • 하혜경 (한국한의학연구원 한약제제연구부) ;
  • 정대영 (상명대학교 화학과) ;
  • 박시원 (상명대학교 화학과)
  • 발행 : 2004.08.01

초록

The present investigation was undertaken to examine the anticancer activity of the methanol extract from Houttuynia cordata on ICR mouse with induced abdominal cancer and L1210 cancer cells. When the methanol extract of Houttuynia cordata (10∼200 $\mu\textrm{g}$/$m\ell$) was administered orally to ICR mouse with abdominal cancer, 47.8% of the best life prolonging effect was obtained. In case of cytotoxicity study (inhibition of cell proliferation) of Houttuynia cordata extract against L1210 cells, $IC_{50}$/ was found to be 62.8 $\mu\textrm{g}$/$m\ell$. In contrast to such considerable toxicity against cancer cell line, the toxicity demonstrated by the identical extract against normal lymphocytes was very meagre as shown to be < 5% compared with 86.5% in case of L1210 cells at the same condition. To get an insight into the reaction mechanism undelying the anticancer activity, $O_2$ion quantity and antioxidant enzyme activities such as superoxide dismiutase (SOD) and glutathione peroxidase (GPx) of L1210 cells in the presence of Houttuynia cordata extract were measured. The increased values of SOD and GPx enzyme activities in addition to the augmented generation of $O_2$ ion in L1210 cells implied that the reactive oxygen species induding $O_2$ion which were presumably induced by Houttuynia cordata extract might have participated in the process of L1210 cells cytotoxicity.

키워드

참고문헌

  1. Hayashi, K., Kamiya, M. and Hayashi, T : Virucidal effects of the steam distillate from Houttuynia cordata and its components on HSV-1 influenza virus and HIV. Planta Medica 61, 237 (1995)
  2. Chang, J .S., Ching, L. C., Chen, C. C., Liu, L.T., Wang, K. C. and Lin, C. C. : Antileukemic activity of bidens pilosa minor (Blume) Sheriff and Houttuynia cordata Thumb. Amer. J. Chin. Med. 29, 303 (2001) https://doi.org/10.1142/S0192415X01000320
  3. Urabe, K., Nakamoto, T., Kawamura, M. and Yasumoto, K. : Effects of Houttuynia cordata and refinery final mosses on the development of offensive odor in porcine small intestine during storage. J. Nutr. Sci. Vitamin. 40, 63 (1994)
  4. 약초의 성분과 이용 (문관심) 과학 백과사전 출판사편, 일월서각 서울 p. 127 (1991)
  5. 서울大學校 天然物科學硏究所 文獻情報學硏究室 編. 東洋醫藥學大典 I p. 282 (2003)
  6. Astrow, A. B. : Rethinking cancer. Lancet 343, 494 (1994) https://doi.org/10.1016/S0140-6736(94)91454-0
  7. Bailer, J. C. and Gormick, H. L. : Cancer undefeated. N. Eng. J. Med. 336, 1569 (1997) https://doi.org/10.1056/NEJM199705293362206
  8. Steel, V. E. : Current mechanistic approaches to the chemoprevention of cancer. J. Biochem. Mol. Biol. 36, 78 (2003)
  9. Lopes, C., Garcia, M., Benavides, F, Shen, J., Conti, C. J., Alvarez, E. and Hajos, S. E. : Multidrug resistance modulators PSC 833 and CsA show differential capacity to induce apoptosis in lymphoid leukemia cell lines independently of their MDR phenotype. Leukem. Res. 27, 413 (2003) https://doi.org/10.1016/S0145-2126(02)00216-3
  10. Ramirez, J. L., Sarries, C., Castro, P. L., Roig, B., Queralt, C. and Escuin, D. : Methylation patterns and k-ras mutations in tumor and pared serum of resected nonsmall cell lung cancer patients. cancer Letters 193, 207 (2002) https://doi.org/10.1016/S0304-3835(02)00740-1
  11. Segura, P. B., Trejo, B. C., Perex, C. E., Taja, C. L., Mariscal, I., Chavex, A., Acuna, C., Salazar, A. M., Lizano, M. and Duenas, G. A. : Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin. Cancer Res. 9, 1596 (2003)
  12. Harden, S. V., Tokumaru, Y., Westra, W. H., Gdoodman, S., Ahrendt, S. A., Yang, S. and Sideransky, D. : Gene promoter hypermethylation in tumors and lymph nodes of stage I lung cancer patients. Clin. Cancer Res. 9, 1370 (2003)
  13. Lee, S. H. : Recognition of DNA damage in Mammals J.Biochem. Mol. Biol. 34, 489 (2001)
  14. Spruck, C. H., Strohmaier, H., Sangfelt,. O., MullerI; H. M., Hubalt, M., Muller, H. E., Marth, C., Widschwendter, M. and Reed, S. I. : hC DC4 gene mutations in Endometrial Cancer. Cancer Res. 62, 4535 (2002)
  15. Palena, S. and Tsang, K. Y. : Differential gene expression profiles in a human T-cell line stimulated with a tumorassociated self peptide versus an enhancement agonist peptide. Clin. cancer Res. 9, 1616 (2003)
  16. Childs, A. C., Phaneuf, S. L., Dirks, A. J., Phillips, T. and Leeuwenburg, C. : Doxorubicin treatment in vivo causes cytochrome c release and cardiomyocytes apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity and Bcl-2 : Bax ratio. Cancer Res. 6, 4592 (2002)
  17. Evans, M. D., Griffith, H. R. and Lunec, J. : Reactive oxygen species and their cytotoxic mechanisms. Advan. Mol. CeII Biol. 20, 25 (1997)
  18. Boyum, A. : Isolation of leukocytes from human blood. Scan.J. Clin. Invest. 21, 9 (1968) https://doi.org/10.3109/00365516809168026
  19. National Cancer Institute USA : Cell Screen KB. Protocol 1600. Cancer Chemother. Rep. (part3) 3, 17 (1972)
  20. Markesbery, W. R. : Oxidative stress hypothesis in Alzheimer disease. Free Radical Bio. Med. 23, 134 (1994) https://doi.org/10.1016/S0891-5849(96)00629-6
  21. McCord, J. and Fridovich, I. : Superoxide dismutase. An enzymatic function for erythrocuprein (heterocuprein).J. Biol. Chem. 244, 6049 (1969)
  22. Maral, J., Puget K. and Michelson, A. M. : Comparative study of superoxide dismutase, catalase, glutathione peroxidase levels in erythrocytes of different animals. Biochem. Biophys. Res. Commun. 77, 1525 (1977) https://doi.org/10.1016/S0006-291X(77)80151-4
  23. Brown, J. M. and Wouters, B. G. : Apoptosis, p53, and tumor cell sensitivity to anticancer agent. Cancer Res. 59, 1391 (1999)
  24. Fulda, S., Sievertes,H., Friesen, C., Herr; I. and Debatin,K. M. : The CD95(APO-1/Fas) System mediates drug induced apoptosis in neuroblastoma cells. Cancer Res. 57, 3823 (1997)
  25. Han, J. W., Duionne, C. A., Kedersha, N. L. and Goldmacher, V. S. : p53 status affects the rate of onset but not the overall extent of doxorubicin induced cell death in rat fibroblasts constituitively expressing c-Myc. Cancer Res. 57, 176 (1997)
  26. Reiter, R. J. : Oxidative processes and antioxidatiye defense mechanism in the aging brain. FASEB J. 9, 526 (1995)
  27. Boonstra, J. and Post, J. A. : Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 337, 1 (2004) https://doi.org/10.1016/j.gene.2004.04.032
  28. Jacobson, M. D. : Reactive oxygen species and programmed cell death. TIBS 21, 83 (1996)