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葡萄成分白藜芦醇通过激活外在和内在途径诱导 DU145 人前列腺癌细胞凋亡。

The grape component piceatannol induces apoptosis in DU145 human prostate cancer cells via the activation of extrinsic and intrinsic pathways.

机构信息

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Republic of Korea.

出版信息

J Med Food. 2009 Oct;12(5):943-51. doi: 10.1089/jmf.2008.1341.

DOI:10.1089/jmf.2008.1341
PMID:19857055
Abstract

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol that is found in grapes, red wine, Rheum undulatum, and the seeds of Euphorbia lagascae. It has been previously reported that piceatannol inhibits the proliferation of a variety of cancer cell types. In the present study, we assessed the effects of piceatannol on the growth of androgen-insensitive DU145 prostate cancer cells at concentrations of 1-10 micromol/L. Piceatannol reduced the viable numbers and increased the numbers of apoptotic DU145 cells in a dose-dependent manner. Western blot analysis revealed that piceatannol increased the protein levels of cleaved caspase-8, -9, -7, and -3 and cleaved poly(ADP-ribose) polymerase (PARP). Piceatannol increased mitochondrial membrane permeability and cytochrome c release from the mitochondria to the cytosol. Piceatannol induced an increase in the levels of truncated Bid, Bax, Bik, Bok, and Fas but caused a decrease in the levels of Mcl-1 and Bcl-xL. Caspase-8 and -9 inhibitors mitigated piceatannol-induced apoptosis. The caspase-8 inhibitor suppressed the piceatannol-induced cleavage of Bid, caspase-3, and PARP. These results indicate that piceatannol induces apoptosis via the activation of the death receptor and mitochondrial-dependent pathways in prostate cancer cells.

摘要

白皮杉醇(反式-3,4,3',5'-四羟基二苯乙烯)是一种多酚,存在于葡萄、红酒、大黄和飞扬草的种子中。先前有报道称,白皮杉醇能抑制多种癌细胞的增殖。在本研究中,我们评估了 1-10μmol/L 浓度的白皮杉醇对雄激素非敏感型 DU145 前列腺癌细胞生长的影响。白皮杉醇以剂量依赖的方式减少了活细胞数量并增加了凋亡的 DU145 细胞数量。Western blot 分析显示,白皮杉醇增加了裂解的 caspase-8、-9、-7 和 -3 以及裂解的多聚(ADP-核糖)聚合酶(PARP)的蛋白水平。白皮杉醇增加了线粒体膜通透性和细胞色素 c 从线粒体向细胞质的释放。白皮杉醇诱导截断 Bid、Bax、Bik、Bok 和 Fas 的水平增加,但导致 Mcl-1 和 Bcl-xL 的水平降低。Caspase-8 和 -9 的抑制剂减轻了白皮杉醇诱导的细胞凋亡。Caspase-8 抑制剂抑制了白皮杉醇诱导的 Bid、caspase-3 和 PARP 的裂解。这些结果表明,白皮杉醇通过激活前列腺癌细胞中的死亡受体和线粒体依赖性途径诱导细胞凋亡。

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