Resveratrol-induced autophagocytosis in ovarian cancer cells
Resveratrol-induced autophagocytosis in ovarian cancer cells
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DOI：
10.1158/0008-5472.can-03-2404
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发表时间：
2004-01-15
期刊：
影响因子：
11.2
通讯作者：
Liu, JR
中科院分区：
文献类型：
--
作者：
Opipari, AW;Tan, LJ;Liu, JR
白藜芦醇（3，5，4-三羟基芪）是一种天然植物抗毒素，存在于葡萄、坚果和红酒中，具有抗衰老活性。已经描述了几种分子机制来支持其在体外和体内对细胞的作用。在本研究中，卵巢癌细胞对白藜芦醇的反应进行了探索。白藜芦醇抑制生长，并诱导死亡的五个人卵巢癌细胞系的面板。这种反应与线粒体释放细胞色素c、形成线粒体复合物和半胱天冬酶激活有关。令人惊讶的是，即使有这些细胞凋亡的分子特征，通过光学和电子显微镜分析白藜芦醇处理的细胞，发现形态和超微结构的变化指示自噬，而不是凋亡，死亡。这表明白藜芦醇可以通过两种不同的途径诱导细胞死亡。与白藜芦醇通过非凋亡过程杀死细胞的能力一致，转染以表达高水平抗凋亡蛋白Bcl-x（L）和Bcl-2的细胞与对照细胞对白藜芦醇同样敏感。总之，这些研究结果表明，白藜芦醇通过与凋亡不同的机制诱导卵巢癌细胞的细胞死亡，因此表明它可能为治疗基于无效凋亡的化疗耐药卵巢癌提供杠杆作用。
Resveratrol (3,5,4-trihydroxystilbene), a natural phytoalexin present in grapes, nuts, and red wine, has antineoplastic activities. Several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo. In the present study, the response of ovarian cancer cells to resveratrol is explored. Resveratrol inhibited growth and induced death in a panel of five human ovarian carcinoma cell lines. The response was associated with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation. Surprisingly, even with these molecular features of apoptosis, analysis of resveratrol-treated cells by light and electron microscopy revealed morphology and ultrastructural changes indicative of autophagocytic, rather than apoptotic, death. This suggests that resveratrol can induce cell death through two distinct pathways. Consistent with resveratrol's ability to kill cells via nonapoptotic processes, cells transfected to express high levels of the antiapoptotic proteins Bcl-x(L) and Bcl-2 are equally sensitive as control cells to resveratrol. Together, these findings show that resveratrol induces cell death in ovarian cancer cells through a mechanism distinct from apoptosis, therefore suggesting that it may provide leverage to treat ovarian cancer that is chemoresistant on the basis of ineffective apoptosis.