Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 Murine Bladder Tumor cells
- 110 Downloads
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 genusCapsicum, 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 AcDEVD-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.
Key wordsCapsaicin Bladder cancer Apoptosis Reactive oxygen species Bcl-2 Cytochromec release Caspase-3
- Denis, G., Humblet, C., Verlaet, M., Boniver, J., and Defresne, M. P., p53, Bax and Bcl-2in vivo expression in the murine thymus after apoptogenic treatments.Anticancer Res., 18, 3315–3321 (2000).Google Scholar
- 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.Cancer Res., 64, 1071–1078 (2004).PubMedCrossRefGoogle Scholar
- 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.Google Scholar