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Capsaicin-Induced Apoptosis and Reduced Release of Reactive Oxygen Species in MBT-2 Murine Bladder Tumor Cells

Lee, Ji-Seon    (College of Pharmacy, Yeungnam University   ); Chang, Jong-Sun    (College of Pharmacy, Yeungnam University   ); Lee, Ji-Youl    (Department of Urology, College of Medicine, Catholic University of Korea   ); Kim, Jung-Ae    (College of Pharmacy, Yeungnam University  );
  • 초록

    Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.

  • 주제어

    Capsaicin .   Bladder cancer .   Apoptosis .   Reactive oxygen species .   Bcl-2 .   Cytochrome c release .   Caspase-3.  

  • 참고문헌 (33)

    1. Borner, C., The BcI-2 protein family: sensors and checkpoints for Iife-or-death decisions. Mol. Immunol., 39, 615-647 (2003) 
    2. Cerutti, P. A., Prooxidant states and tumor promotion. Science, 227, 375-381 (1985) 
    3. De Ridder, D., Chandiramani, V., Dasgupta, P, Van Poppel, H., Baert, L., and Fowler, C. J., Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J. Urol., 158, 2087-2092 (1997) 
    4. Kang, H. J., Soh, Y., Kim, M. S., Lee, E. J., Surh, Y. J., Kim, H. R., Kim, S. H., and Moon, A., Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in rastransformed human breast epithelial cells. Int. J. Cancer, 103, 475-482 (2003) 
    5. Lee, Y. S., Kang, Y. S., Lee, J. S., Nikolova, S., and Kim, J. A., Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Rad. Res., 38, 405-412 (2004) 
    6. Sternberg, C. N., A critical review of the management of bladder cancer. Crit. Rev. Oncol. Hematol., 31, 193-207 (1999) 
    7. Surh, Y. J. and Lee, S. S., Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci., 56,1845-1855 (1995) 
    8. Suzuki, T. and Iwai, K., Constitution of red pepper species: chemistry, biochemistry, pharmacology, and food science of the pungent principle of Capsicum species, in: A. Brosi (Ed.), The Alkaloides, 23, Academic Press, New York, 1994, pp. 227-299 
    9. Jemal, A., Murray, T., Samuels, A., Ghafoor, A, Ward, E., and Thun, M. J., Cancer statistics, 2003. CA Cancer J. Clin., 53, 5-26 (2003) 
    10. Lee, Y. S., Kwon, E. J., Jin, D. Q., Park, S. H., Kang, Y. S., Huh, K., and Kim, J. A. Redox status-dependent regulation of cyclooxygenases mediates the capsaicin-induced apoptosis in human neuroblastoma cells. J. Environ. Pathol. Toxicol. Oncol., 21,113-120 (2002) 
    11. Gross, A., McDonnell, J. M., and Korsmeyer, S. J., BCL-2 family members and the mitochondria in apoptosis. Genes Dev., 13, 1899-1911 (1999) 
    12. Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65, 55-63 (1983) 
    13. Haunstetter, A. and Izumo, S., Apoptosis; basic mechanism and implications for cardiovascular disease. Circ. Res., 82, 1111-1129 (1998) 
    14. Bombeli, T., Karsan, A., Tait, J. F., and Harlan, J. M., Apoptotic vascular endothelial cells become procoagulant. Blood, 89, 2429-2442 (1997) 
    15. Denis, G., Humblet, C., Verlaet, M., Boniver, J., and Defresne, M. P., p53, Sax and BcI-2 in vivo expression in the murine thymus after apoptogenic treatments. Anticancer Res., 18, 3315-3321 (2000) 
    16. Green, D. R. and Reed, J. C., Mitochondria and apoptosis. Science, 281, 1309-1312 (1998) 
    17. Liu, X., Kim, G. N., Yang, J., Jemmerson, R., and Wang, X., Induction of apoptotic program in cell-free extracts; Requirement for dATP and cytochrome c. Cell, 86, 147-157 (1996) 
    18. Lee, Y. S., Nam, D. H., and Kim, J. A., Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett., 161, 121-130 (2000) 
    19. Surh Y. J., More than spice: capsaicin in hot chili peppers makes tumor cells commit suicide. J. Natl. Cancer Inst. 94, 1263-1265 (2002) 
    20. Szatrowski, T. P. and Nathan, C. F., Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res., 51, 794-798 (1991) 
    21. Tanaka, T., Kohno, H., Sakata, K., Yamada, Y., Hirose, Y., Sugie, S., and Mori, H., Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline I-oxideinduced rat tongue carcinogenesis. Carcinogenesis, 23, 1361-1367 (2002) 
    22. Surh, Y. J., Lee E., and Lee, J. M., Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutat. Res., 402, 259-267 (1998) 
    23. Jung, M. Y., Kang, H. J., and Moon, A., Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett., 165, 139-145 (2001) 
    24. Lamm, D. L., Superficial bladder cancer. Curr. Treat. Options Oncol., 3, 403-411 (2002) 
    25. Pook, S. H., Esuvaranathan, K., and Mahendran, R., N-Acetylcysteine augments the cellular redox changes and cytotoxic activity of internalized mycobacterium bovis in human bladder cancer cells. J. Urol., 168, 780-785 (2002) 
    26. Tu, Y., Xu, F. H., Liu, J., Vescio, R., Berenson, J., Fady, C., and Lichtenstein, A., Upregulated expression of BCL-2 in multiple myeloma cells induced by exposure to doxorubicin, etoposide, and hydrogen peroxide. Blood, 88, 1805-1812 (1996) 
    27. Zhang, J., Nagasaki, M., Tanaka, Y, and Morikawa, S., Capsaicin inhibits growth of adult T-cell leukemia cells. Leuk. Res., 27, 275-283 (2003) 
    28. Cordell, G. A. and Araujo, O. E., Capsaicin: identification, nomenclature, and pharmacotherapy. Ann. Pharmacother., 27, 330-336 (1993) 
    29. Galati, G. and O'Brien, P. J., Cytoprotective and anticancer properties of coenzyme Q versus capsaicin. Biofactors, 18, 195-205 (2003) 
    30. Herrmann, M., Lorenz, H. M., Vollm, R., Grunkem, M., Woithm, W., and Kaldenm, J. R., A rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic Acids Res., 22, 5506-5507 (1994) 
    31. Tanaka, T., Kohno, H., Sakata, K., Yamada, Y., Hirose, Y., Sugie, S., and Mori, H., Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline I-oxide-induced rat tongue carcinogenesis. Carcinogenesis, 23, 1361-1367 (2002) 
    32. Ito, K., Nakazato, T., Yamato, K., Miyakawa, Y., Yamada, T., Hozumi, N., Segawa, K., Ikeda, Y., and Kizaki, M., Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Gancer Res., 64, 1071-1078 (2004) 
    33. Akaza, H., Hinotsu, S., Aso, Y., Kakizoe, T., and Koiso, K., Bacillus Calmette-Guerin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results. Cancer, 75, 552-559 (1995) 
  • 이 논문을 인용한 문헌 (5)

    1. Kwak, Chung-Shil ; Kim, Mee-Yeon ; Lee, Mee-Sook 2005. "Antioxidative Effect of Plant Food Mixtures in Rat Fed on High Fat-High Cholesterol Diet" 韓國營養學會誌 = The Korean journal of nutrition., 38(5): 352~363     
    2. 2007. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 30(1): 28~33     
    3. Kim, Sun Young ; Lee, You Jin ; Park, Eun Hye ; Yi, Ho Keun ; Jo, Dae Sun ; Kim, Jung Soo ; Hwang, Pyoung Han 2008. "Capsaicin induced apoptosis and the enhanced anticancer effect of anticancer drugs in cancer cells" Korean journal of pediatrics, 51(3): 307~314     
    4. 2008. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 31(5): 606~610     
    5. Kim, Hyo-Eun ; Jang, Min-Jeong ; Lim, Seung-Hyun ; Kim, Hyo-Rim ; Kim, Soon-Young ; Lee, Gun-Joo ; Kim, Jong-Sik 2010. "Analysis of p53-Dependency of Differentially Expressed Genes by Capsaicin in Human Colorectal Cancer Cell" 생명과학회지 = Journal of life science, 20(2): 213~218     

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