Resveratrol-induced apoptosis in human breast cancer cells is mediated primarily through the caspase-3-dependent pathway
Resveratrol-induced apoptosis in human breast cancer cells is mediated primarily through the caspase-3-dependent pathway
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DOI：
10.1016/j.arcmed.2007.09.003
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发表时间：
2008-02-01
影响因子：
7.7
通讯作者：
Al-Attyiah, Rajaa
中科院分区：
文献类型：
--
作者：
Alkhalaf, Moussa;El-Mowafy, Abdulla;Al-Attyiah, Rajaa
背景白藜芦醇（RSVL）是一种无毒的天然化合物，广泛存在于各种植物中，具有抗氧化和抗炎作用，正成为一种有效的化学预防和抗癌药物。最近，我们证明了RSVL诱导的几种人癌细胞系的凋亡与促凋亡的116 kDa聚（ADP-核糖）聚合酶蛋白（PARP）裂解成其89 kDa片段有关。Western blotting检测caspase-3和PARP蛋白表达水平。用caspase-3比色底物DEVD-pNA分析caspase活性。Annexin V-FITC-propidium iodide双染法检测凋亡细胞。我们发现RSVL以剂量和时间依赖性方式将未成熟的caspase-3（35 kDa）切割成活性片段（p12，p17，p20）。此外，RSVL显著增加细胞中的caspase-3活性（5倍）。有趣的是，RSVL诱导的PARP裂解和凋亡可通过抑制caspase-3而特异性阻断。总的来说，这些数据表明RSVL激活caspase-3是MDA-MB-231细胞中PARP降解和诱导细胞凋亡所必需的，并为RSVL的作用提供了额外的见解，从而证实了RSVL对人乳腺癌的化学预防潜力。(C)2008年IMSS。爱思唯尔公司出版
Background. Resveratrol (RSVL), a nontoxic natural compound found in a wide variety of plants with known antioxidant and anti-inflammatory properties, is emerging as a potent chemopreventive and anticancer drug. Recently, we demonstrated that RSVL-induced apoptosis in several human cancer cell lines was associated with cleavage of the proapoptotic 116 kDa poly(ADP-ribose) polymerase protein (PARP) into its 89-kDa fragment.Methods. Western blotting was used to check the levels of caspase-3 and PARP proteins. The caspase activity was analyzed with the caspase-3 colorimetric substrate DEVD-pNA. Apoptotic cells were quantified by annexin V-FITC-propidium iodide double staining.Results. We show that RSVL cleaved the immature caspase-3 (35 kDa) into the active fragments (p12, p17, p20) in a dose- and time-dependent manner. In addition, RSVL markedly increased caspase-3 activity (5-fold) in cells. Interestingly, RSVL-induced PARP cleavage and apoptosis was blocked specifically by inhibiting caspase-3.Conclusions. Collectively, the data suggest that caspase-3 activation by RSVL is required for PARP degradation and induction of apoptosis in MDA-MB-231 cells and provide additional insights into the action of RSVL, thus substantiating the chemopreventive potential of RSVL against human breast cancer. (C) 2008 IMSS. Published by Elsevier Inc.