Chen Chung-Yi, Liu Tsan-Zon, Tseng Wei-Chang, Lu Fung-Jou, Hung Ray-Ping, Chen Chi-Hung, Chen Ching-Hsein
School of Medicine and Health Sciences, Fooyin University, Kaohsiung Hsien 831, Taiwan.
Food Chem Toxicol. 2008 Aug;46(8):2694-702. doi: 10.1016/j.fct.2008.04.024. Epub 2008 Apr 27.
(-)-Anonaine has been shown to have some anticancer activities, but the mechanisms of (-)-anonaine inducing cell death of human cancer cells is not fully understood. We investigated the mechanisms of apoptosis induced by (-)-anonaine in human HeLa cancer cells. Treatment with (-)-anonaine induces dose-dependent DNA damage that is correlated with increased intracellular nitric oxide, reactive oxygen species, glutathione depletion, disruptive mitochondrial transmembrane potential, activation of caspase 3, 7, 8, and 9, and poly ADP ribose polymerase cleavage. Our data indicate that (-)-anonaine up-regulated the expression of Bax and p53 proteins in HeLa cancer cells. The apoptosis and expression of Bax induced by (-)-anonaine could be inhibited when the HeLa cells were pretreated with Boc-Asp(OMe)-fmk, which is a broad caspases inhibitor. There was no obvious DNA damage in the (-)-anonaine-treated Madin-Darby canine kidney and Vero cell lines. Both Madin-Darby canine kidney and Vero cell lines are kidney epithelial cellular morphology. These results suggest that (-)-anonaine might be considered a potent compound for chemotherapy against cervical cancer or a health food supplement for cancer chemoprevention.
（-）-去甲乌药碱已被证明具有一些抗癌活性，但（-）-去甲乌药碱诱导人癌细胞死亡的机制尚未完全明确。我们研究了（-）-去甲乌药碱在人宫颈癌细胞HeLa中诱导凋亡的机制。用（-）-去甲乌药碱处理会诱导剂量依赖性的DNA损伤，这与细胞内一氧化氮增加、活性氧生成、谷胱甘肽耗竭、线粒体跨膜电位破坏、半胱天冬酶3、7、8和9的激活以及聚ADP核糖聚合酶的裂解相关。我们的数据表明，（-）-去甲乌药碱上调了HeLa癌细胞中Bax和p53蛋白的表达。当用泛半胱天冬酶抑制剂Boc-Asp（OMe）-fmk预处理HeLa细胞时，（-）-去甲乌药碱诱导的凋亡和Bax表达可被抑制。在经（-）-去甲乌药碱处理的Madin-Darby犬肾细胞和Vero细胞系中未观察到明显的DNA损伤。Madin-Darby犬肾细胞和Vero细胞系均为肾上皮细胞形态。这些结果表明，（-）-去甲乌药碱可能被视为一种用于宫颈癌化疗的有效化合物或用于癌症化学预防的健康食品补充剂。
