Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
Mol Med Rep. 2012 Feb;5(2):585-91. doi: 10.3892/mmr.2011.688. Epub 2011 Nov 24.
Capsaicin and resveratrol are strong chemopreventive agents with promising human consumption safety records and anticarcinogenic activities. However, the mechanism by which they induce apoptosis in tumor cells remains to be defined. In this study, we examined the role of nitric oxide (NO•) during apoptosis induced by these agents in A375 human melanoma cells. Capsaicin and resveratrol, alone or in combination, inhibited cell growth and promoted apoptosis by the elevation of NO• in A375 cells. Increased NO• production following treatment stimulated p53 and triggered mitochondrial apoptotic events by inducing conformational changes in Bax and Bcl-2 with subsequent release of cytochrome c and activation of caspase 9 and 3. Caspase 8 activation concurrently appeared to be mediated by death receptor processing and downstream caspases. Collectively, our data suggest that capsaicin and resveratrol activate the mitochondrial and death receptor pathways, working together to induce apoptosis in A375 cells, and indicate that NO• could be considered a potential target for improvement of the effectiveness of melanoma treatment.
辣椒素和白藜芦醇是具有强大化学预防作用的物质，它们具有良好的人类消费安全性记录和抗癌活性。然而，它们诱导肿瘤细胞凋亡的机制仍有待确定。在这项研究中，我们研究了一氧化氮（NO•）在这些物质诱导 A375 人黑素瘤细胞凋亡过程中的作用。辣椒素和白藜芦醇单独或联合使用，通过增加 A375 细胞中的 NO•来抑制细胞生长并促进细胞凋亡。治疗后 NO•产生增加刺激 p53，并通过诱导 Bax 和 Bcl-2 的构象变化，随后释放细胞色素 c 和激活 caspase 9 和 3，引发线粒体凋亡事件。同时，caspase 8 的激活似乎是通过死亡受体的加工和下游 caspase 介导的。总的来说，我们的数据表明，辣椒素和白藜芦醇激活线粒体和死亡受体途径，共同诱导 A375 细胞凋亡，并表明 NO•可以被认为是提高黑素瘤治疗效果的潜在靶点。
