Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome c release and apoptosis
Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome c release and apoptosis
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DOI：
10.1002/ijc.10202
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发表时间：
2002-04-10
影响因子：
6.4
通讯作者：
Pandol, SJ
中科院分区：
文献类型：
--
作者：
Mouria, M;Gukovskaya, AS;Pandol, SJ
越来越多的证据表明，食物来源的多酚对癌症有有益的影响。我们的目的是确定这些化合物对胰腺癌的作用效果和作用机制。我们在裸鼠模型中测量了槲皮素对胰腺癌的作用。我们还研究了槲皮素、芦丁、反式白藜芦醇和染料木黄酮对胰腺癌细胞凋亡和潜在信号转导的影响。在胰腺癌模型中，槲皮素可降低原发肿瘤生长，增加细胞凋亡并防止转移。在体外，槲皮素和反式白藜芦醇，但不是芦丁，显着增强细胞凋亡，引起线粒体去极化和细胞色素c释放，然后半胱天冬酶-3激活。此外，槲皮素和反式白藜芦醇的组合对线粒体细胞色素c释放和半胱天冬酶-3活性的影响大于预期的加性响应。线粒体渗透性转变的抑制阻止了多酚引起的细胞色素c释放、caspase-3激活和细胞凋亡。核因子-kappaB活性被槲皮素和反式白藜芦醇抑制，但不被染料木黄酮抑制，这表明该转录因子不是多酚类物质对细胞凋亡影响的唯一介质。结果表明，食物来源的多酚抑制胰腺癌的生长，并通过诱导线粒体功能障碍，导致细胞色素c释放，半胱天冬酶激活和细胞凋亡，防止转移。(C)2002 Wiley-Liss，Inc.
There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-kappaB activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis. (C) 2002 Wiley-Liss, Inc.