Archives of Pharmacal Research

  • 제27권12호
  • /
  • Pages.1253-1257
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  • 2004
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Apoptosis Inducing Effects of 6-Methoxydihydrosanguinarine in HT29 Colon Carcinoma Cells

  • Lee, Yong-Jin (College of Pharmacy and MeRRI, Wonkwang University) ;
  • Yin, Hu-Quan (College of Pharmacy and MeRRI, Wonkwang University) ;
  • Kim, Young-Ho (College of Pharmacy, Chungnam National University) ;
  • Li, Guang-Yong (College of Pharmacy and MeRRI, Wonkwang University) ;
  • Lee , Byung-Hoon (College of Pharmacy and MeRRI, Wonkwang University)
  • 발행 : 2004.01.01
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초록

6-Methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid derived from the methanol extracts of Hylomecon hylomeconoides, showed a dose-dependent effect at 1-10 ${\mu}M$ on causing apoptotic cell death in HT29 colon carcinoma cells $(IC_{50} = 5.0{\pm}0.2 {\mu}M)$. Treatment of HT-29 cells with 6ME resulted in the formation of internucleosomal DNA fragmentation. Treatment of the cells with 6ME caused activation of caspase-3, -8 and 9 protease and subsequent proteolytic cleavage of poly(ADP-ribose)polymerase. 6ME increased the expression of p53 and Bax and decreased the expression of Bid. These results indicate that p53 and proapoptotic Bcl-2 family proteins might participate in the antiproliferative activity of 6ME in HT29 cells.

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참고문헌

  1. Chen, J. J., Chang, Y. L., Teng, C. M., Lin, W. Y., Chen, Y. C., and Chen, I. S., A new tetrahydroprotoberberine N-oxide alkaloid and anti-platelet aggregation constituents of Corydalis tashiroi. Planta Med., 67, 423-427 (2001) https://doi.org/10.1055/s-2001-15820
  2. Cho, Y. S., Phytochemical constituents of Hylomecon hylomeconoides and their activities on neurotransmitter-metabolizing enzymes. Thesis: Chungnam National University (2001)
  3. Devitt, G. P., Creagh, E.M., and Gotter, T. G., The antioxidant 4b,5,9b,10-tetrahydroindeno[l,2-b]indole inhibits apoptosis by preventing caspase activation following mitochondrial depolarization. Biochem. Biophys. Res. Comm., 264, 622-629 (1999). https://doi.org/10.1006/bbrc.1999.1576
  4. Giardiello, F. M., Hamilton, S. R., Krush, A. J., Piantadosi, S., Hylind, L. M., Celano, P., Booker, S. V., Robinson, C. R., and Offerhaus, G. J., Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N. Engl. J. Med., 328, 1313-1316 (1993) https://doi.org/10.1056/NEJM199305063281805
  5. Greenlee, R. T., Murray, T., Bolden, S., and Wingo, P A., Cancerstatistics, 2000. CA Cancer J. Clin., 50, 7-33 (2000) https://doi.org/10.3322/canjclin.50.1.7
  6. Herr, I. and Debatin, K. M., Cellular stress response and apoptosis in cancertherapy. Blood, 98, 2603-2614 (2001) https://doi.org/10.1182/blood.V98.9.2603
  7. Janicke, R. U., Sprengart, M. L., Wati, M. R., and Porter, A. G., Caspase-3 is requiredfor DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem., 273, 9357-936 (1998) https://doi.org/10.1074/jbc.273.16.9357
  8. Juo, P., Kuo, C. J., Yuan, J., and Blenis, J., Essential requirementfor caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr. Biol., 8, 1001-1008 (1998) https://doi.org/10.1016/S0960-9822(07)00420-4
  9. Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P. H., and Peter, M. E., Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a deathinducing signaling complex (DISC) with the receptor. EMBO J., 14, 5579-5588 (1995)
  10. Korsmeyer, S. J., Wei, M. C., Saito, M., Weiler, S., Oh, J., and Schlesinger, P. H., Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell. Death. Differ., 7, 1166-1173 (2000) https://doi.org/10.1038/sj.cdd.4400783
  11. Lowe, S. W., Ruley, H. E., Jacks,T., and Housman, D. E., 53dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell, 74, 957-967 (1993) https://doi.org/10.1016/0092-8674(93)90719-7
  12. Monks, A, Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A, Gray-Goodrich, M., Campbell, H., Mayo, J., and Boyd, M., Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer lnst., 83, 757-766 (1991) https://doi.org/10.1093/jnci/83.11.757
  13. Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., ORourke, K., Shevchenko, A, Ni, J., Scaffidi, C., Bretz, J. D., Zhang, M., Gentz, R., Mann, M., Krammer, P. H., Peter, M. E., and Dixit, V. M., FLICE, a novel FADD-homologous IC/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) deathinducing signaling complex. Cell, 85, 817-827 (1996) https://doi.org/10.1016/S0092-8674(00)81266-0
  14. Steinbach, G., Lynch, P. M., Phillips, R. K., Wallace, M. H., Hawk, E., Gordon, G. B., Wakabayashi, N., Saunders, B., Shen, Y., Fujimura, T., Su, L. K., and Levin, B., The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Mad., 342, 1946-1952 (2000) https://doi.org/10.1056/NEJM200006293422603