The Grape Component Piceatannol Induces Apoptosis in DU145 Human Prostate Cancer Cells via the Activation of Extrinsic and Intrinsic Pathways
The Grape Component Piceatannol Induces Apoptosis in DU145 Human Prostate Cancer Cells via the Activation of Extrinsic and Intrinsic Pathways
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DOI：
10.1089/jmf.2008.1341
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发表时间：
2009-10-01
影响因子：
2.4
通讯作者：
Park, Jung Han Yoon
中科院分区：
文献类型：
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作者：
Kim, Eun Ji;Park, Heesook;Park, Jung Han Yoon
Piceatannol（反式 3,4,30,50-四羟基二苯乙烯）是一种多酚，存在于葡萄、红酒、波状大黄和大戟种子中。此前已有报道，白皮杉醇可抑制多种癌细胞类型的增殖。在本研究中，我们评估了浓度为1-10 μmol/L的白皮杉醇对雄激素不敏感的DU145前列腺癌细胞生长的影响。白皮杉醇以剂量依赖性方式减少活细胞数量并增加凋亡 DU145 细胞的数量。蛋白质印迹分析显示，白皮杉醇增加了裂解的 caspase-8、-9、-7 和 -3 以及裂解的聚（ADP-核糖）聚合酶 (PARP) 的蛋白质水平。 Piceatannol 增加线粒体膜通透性和细胞色素 c 从线粒体到细胞质的释放。 Piceatannol 诱导截短的 Bid、Bax、Bik、Bok 和 Fas 水平增加，但导致 Mcl-1 和 Bcl-xL 水平降低。 Caspase-8 和 -9 抑制剂可减轻白皮杉醇诱导的细胞凋亡。 caspase-8 抑制剂抑制白皮杉醇诱导的 Bid、caspase-3 和 PARP 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来诱导细胞凋亡。
Piceatannol (trans-3,4,30,50-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 mu mol/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.