绿茶中的茶多酚可以抑制肿瘤增殖、诱导癌细胞程序性死

 

Role of Bax/Bcl-2 family members in green tea polyphenol induced necroptosis of p53-deficient Hep3B cells

 

翻译:蓝山

 

绿茶多酚(GTP)是最有前途的化学预防药物之一;它可以通过p53依赖的细胞信号通路抑制癌细胞增殖和诱导凋亡。不幸的是,许多肿瘤细胞缺乏p53功能,而GTPp53缺失/突变型癌细胞的影响知之甚少。

 

为了了解GTP治疗的p53-特异/突变型癌细胞的p53-独立机制,我们现在研究了GTP诱导的人肝癌细胞的细胞毒性(p53缺失)

 

结果表明,GTP可诱导BaxBak活化,细胞色素c释放,Caspase激活,以及Hep3B细胞的程序性坏死。BaxBak是线粒体渗透性过渡孔(MPTP)的两个关键分子,被GTP相互依赖激活,在线粒体上具有易位和homo- oligomBaxBak诱导细胞色素c释放。重要的是,在Hep3B(Bax/)Hep3B(Bak/)细胞,细胞色素c的释放和程序性坏死减少。

 

 

此外,Bcl-2的过表达可以减少GTP诱导的细胞色素C释放和程序性坏死。结果表明,GTP诱导的程序性坏死是由独立于p53的通路调控的,这与BaxBak对线粒体的转运、细胞色素c的释放以及caspase的激活有关。

 

 

参考文献

Bax/Bcl-2家族成员在绿茶多酚诱导p53缺失的Hep3B细胞的程序性细胞坏死中的作用

Role of Bax/Bcl-2 family members in green tea polyphenol induced necroptosis of p53-deficient Hep3B cells

 

Green tea polyphenol (GTP) is one of the most promising chemopreventive agent for cancer; it can inhibit cancer cell proliferation and induce apoptosis through p53-dependent cell signaling pathways. Unfortunately, many tumor cells lack the functional p53, and little is known about the effect of GTP on the p53-deficient/mutant cancer cells. To understand the p53-independent mechanisms in GTP-treated p53-dificient/mutant cancer cells, we have now examined GTP-induced cytotoxicity in human hepatoma Hep3B cells (p53-deficient). The results showed that GTP could induce Bax and Bak activation, cytochrome c release, caspase activation, and necroptosis of Hep3B cells. Bax and Bak, two key molecules of mitochondrial permeability transition pore (MPTP), were interdependently activated by GTP, with translocation and homo-oligomerization on the mitochondria. Bax and Bak induce cytochrome c release. Importantly, cytochrome c release and necroptosis were diminished in Hep3B cells (Bax/) and Hep3B cells (Bak/). Furthermore, overexpression of Bcl-2 could ameliorate GTP-induced cytochrome c release and necroptosis. Together, the findings suggested that GTP-induced necroptosis was modulated by the p53-independent pathway, which was related to the translocation of Bax and Bak to mitochondria, release of cytochrome c, and activation of caspases.

 

https://link.springer.com/article/10.1007/s13277-014-2064-0