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茶黄素通过调节人前列腺癌PC-3细胞中p21waf1/cip1、cdc25C和细胞周期蛋白B的表达诱导G2/M期阻滞。

Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells.

作者信息

Prasad Sahdeo, Kaur Jaspreet, Roy Preeti, Kalra Neetu, Shukla Yogeshwer

机构信息

Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow 226001, India.

出版信息

Life Sci. 2007 Oct 13;81(17-18):1323-31. doi: 10.1016/j.lfs.2007.07.033. Epub 2007 Sep 15.

Abstract

Cancer of the prostate gland (PCA) is the most common invasive malignancy and is the second leading cause of cancer-related death in males. The polyphenolic constituents of black tea have gained considerable attention as chemopreventive agents. Many studies have shown that black tea reduces the risk of several cancer types. In the present study, we studied the effect of a black tea polyphenol, theaflavin (TF), on cellular proliferation and cell death in the human prostate cancer cell line, PC-3. We showed that TF inhibits cell proliferation in a dose- and time-dependent manner. Studies on cell cycle progression have shown that the anti-proliferative effect of TF is associated with an increase in the G2/M phase of PC-3 cells. Western blot results showed that TF-induced G2/M phase arrest was mediated through the inhibition of cyclin-regulated signaling pathways. TF induces cyclin kinase inhibitor p21(waf1/cip1) expression and inhibits cdc25C and cyclin B expression. Increased exposure time to TF caused apoptosis of PC-3 cells, which was associated with up-regulation of the pro-apoptotic proteins Bax, caspase-3 and caspase-9 and down-regulation of anti-apoptotic protein Bcl-2. The role of caspase-induced apoptosis was further confirmed by a reduction in mitochondria membrane potential and the appearance of a DNA laddering pattern. Thus, it can be concluded that TF acts as an effective anti-proliferative agent by modulating cell growth regulators in prostate cancer cells.

摘要

前列腺癌(PCA)是最常见的侵袭性恶性肿瘤,是男性癌症相关死亡的第二大原因。红茶中的多酚成分作为化学预防剂受到了广泛关注。许多研究表明,红茶可降低多种癌症类型的风险。在本研究中,我们研究了红茶多酚茶黄素(TF)对人前列腺癌细胞系PC-3细胞增殖和细胞死亡的影响。我们发现TF以剂量和时间依赖性方式抑制细胞增殖。对细胞周期进程的研究表明,TF的抗增殖作用与PC-3细胞G2/M期的增加有关。蛋白质印迹结果表明,TF诱导的G2/M期阻滞是通过抑制细胞周期蛋白调节的信号通路介导的。TF诱导细胞周期蛋白激酶抑制剂p21(waf1/cip1)表达,并抑制cdc25C和细胞周期蛋白B的表达。延长TF暴露时间会导致PC-3细胞凋亡,这与促凋亡蛋白Bax、半胱天冬酶-3和半胱天冬酶-9的上调以及抗凋亡蛋白Bcl-2的下调有关。线粒体膜电位降低和DNA梯状条带的出现进一步证实了半胱天冬酶诱导的凋亡作用。因此,可以得出结论,TF通过调节前列腺癌细胞中的细胞生长调节因子,作为一种有效的抗增殖剂发挥作用。

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