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表没食子儿茶素没食子酸酯在体外Cd2+存在下对PC-3细胞的细胞毒性研究。

Investigations of the cytotoxicity of epigallocatechin-3-gallate against PC-3 cells in the presence of Cd2+ in vitro.

作者信息

Zhang Lan-cui, Yu Hai-ning, Sun Shi-li, Yang Jun-guo, He Guo-qing, Ruan Hui, Shen Sheng-rong

机构信息

Hua Jia Chi Campus, Zhejiang University, Hangzhou 310029, PR China.

出版信息

Toxicol In Vitro. 2008 Jun;22(4):953-60. doi: 10.1016/j.tiv.2008.02.005. Epub 2008 Feb 15.

Abstract

The epidemiological studies and recent data have provided convinced evidence that green tea and its major constituent epigallocatechin gallate (EGCG) might have the potential to lower the risk of cancers in humans. Metal ions, such as zinc and cadmium, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. EGCG can satisfactorily exhibit complex chemistry with metal ions because of multiple hydroxyl states, which in turn changes their bioactivities and metabolism pathways. This paper presents the results of an investigation of the cytotoxicity of EGCG against PC-3 prostate cancer cells in the presence and absence of Cd2+ in vitro. The results showed that both EGCG and Cd2+ suppressed viability and clonegenecity of PC-3 cells, and the suppression effect was enhanced when EGCG added with Cd2+. Although Cd2+ up-regulated the 67 kDa laminin receptor (67LR), which is a migration-associated protein, the cell migration ability was not significantly increased after each treatment. We also found that EGCG and Cd2+ directly interacted with mitochondrial, and the mixture of EGCG and Cd2+ (EGCG+Cd2+) significantly caused loss of the mitochondrial membrane potential, decrease of the ATP content and activation of caspase-9 compared with EGCG treated alone. Taken together, these findings suggest that Cd2+ enhanced the cytotoxicity of EGCG to PC-3 cells by up-regulating the 67LR and the mitochondria-mediated apoptosis pathway.

摘要

流行病学研究及近期数据已提供确凿证据,表明绿茶及其主要成分表没食子儿茶素没食子酸酯(EGCG)可能具有降低人类患癌风险的潜力。锌和镉等金属离子对我们的健康至关重要,但在缺乏或过量的情况下,它们是诱发包括前列腺癌在内的多种疾病的重要因素。由于EGCG具有多个羟基状态,它能与金属离子发生令人满意的络合反应,进而改变它们的生物活性和代谢途径。本文展示了一项在体外有无Cd2+存在的情况下,EGCG对PC-3前列腺癌细胞细胞毒性的研究结果。结果表明,EGCG和Cd2+均能抑制PC-3细胞的活力和克隆形成能力,且当EGCG与Cd2+同时添加时,抑制效果增强。尽管Cd2+上调了与迁移相关的蛋白——67 kDa层粘连蛋白受体(67LR),但每次处理后细胞迁移能力并未显著增加。我们还发现,EGCG和Cd2+直接与线粒体相互作用,与单独使用EGCG相比,EGCG和Cd2+的混合物(EGCG+Cd2+)显著导致线粒体膜电位丧失、ATP含量降低以及caspase-9激活。综上所述,这些发现表明,Cd2+通过上调67LR和线粒体介导的凋亡途径增强了EGCG对PC-3细胞的细胞毒性。

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