Department of Research Center, Dong Nam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
Int J Oncol. 2012 Nov;41(5):1628-34. doi: 10.3892/ijo.2012.1615. Epub 2012 Aug 31.
Resveratrol (3,4',5 tri-hydroxystilbene), a natural plant polyphenol, has gained interest as a non-toxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. Several studies were undertaken to obtain synthetic analogues of resveratrol with potent anticancer activity. The aim of the present study was to investigate the effect of HS-1793 as a new resveratrol analog on apoptosis via the mitochondrial pathway in murine breast cancer cells. A pharmacological dose (1.3-20 µM) of HS-1793 exerted a cytotoxic effect on murine breast cancer cells resulting in apoptosis. HS-1793-mediated cytotoxicity in FM3A cells by several apoptotic events including mitochondrial cytochrome c release, activation of caspase-3 and PARP occurred. In addition, HS-1793 induced collapse of ∆Ψm and enhanced AIF and Endo G release from mitochondria while undergoing apoptosis. These results demonstrate that the cytotoxicity by HS-1793 in FM3A cells can mainly be attributed to apoptosis via a mitochondrial pathway by caspase activation or contributions of AIF and Endo G.
白藜芦醇(3,4',5-三羟基二苯乙烯)是一种天然植物多酚,作为一种无毒的化学预防剂,能够诱导多种癌症类型的肿瘤细胞死亡,因此受到关注。已经进行了几项研究来获得具有强大抗癌活性的白藜芦醇合成类似物。本研究的目的是研究 HS-1793 作为一种新的白藜芦醇类似物通过线粒体途径在小鼠乳腺癌细胞中诱导细胞凋亡的作用。药理学剂量(1.3-20µM)的 HS-1793 对小鼠乳腺癌细胞产生细胞毒性作用,导致细胞凋亡。HS-1793 通过多种细胞凋亡事件,包括线粒体细胞色素 c 释放、半胱天冬酶-3 和 PARP 的激活,介导 FM3A 细胞的细胞毒性作用。此外,HS-1793 在诱导细胞凋亡的过程中诱导 ∆Ψm 崩溃并增强 AIF 和 Endo G 从线粒体中的释放。这些结果表明,HS-1793 在 FM3A 细胞中的细胞毒性主要归因于通过半胱天冬酶激活或 AIF 和 Endo G 的贡献的线粒体途径的细胞凋亡。