Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells
Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells
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DOI：
10.1021/jf800175a
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发表时间：
2008-06-25
影响因子：
6.1
通讯作者：
Planas, Joana M.
中科院分区：
文献类型：
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作者：
Emilia Juan, M.;Wenzel, Uwe;Planas, Joana M.
反式白藜芦醇是在蓝莓、葡萄和葡萄酒中发现的一种多酚，具有预防癌症的特性。该化合物的低生物利用度提高了其在管腔内容物中的浓度，并成为潜在的结肠癌预防剂。本研究主要探讨其对人大肠癌HT-29细胞的抗增殖和促凋亡作用及其机制。通过基于荧光的技术测量增殖、细胞毒性和凋亡。对反式白藜芦醇剂量依赖性作用的研究显示出抗增殖活性，EC 50值为78.9 +/- 5.4 μ M。孵育24小时后，胱天蛋白酶-3以剂量依赖性方式活化，产生的EC 50值为276.1 +/- 1.7 μ M。细胞凋亡也证实了细胞膜通透性的变化和DNA片段化检测的显微镜观察。反式白藜芦醇对线粒体凋亡途径的活性通过在经历凋亡的细胞的线粒体中产生超氧阴离子来证明。总之，反式白藜芦醇在HT-29中抑制细胞增殖而无细胞毒性并诱导细胞凋亡。本研究结果为反式白藜芦醇通过ROS依赖的凋亡途径对结直肠癌的抗肿瘤作用提供了证据。
trans-Resveratrol is a polyphenol found in blueberries, grapes, and wine with cancer chernopreventive properties. The low bioavailability of this compound enhances its concentration in the luminal content and becomes a potential chernopreventive agent against colon cancer. In the present study, the antiproliferative and pro-apoptotic effects on the human colorectal carcinoma HT-29 cells as well as the mechanisms underlying these effects were examined. Proliferation, cytotoxicity, and apoptosis were measured by fluorescence-based techniques. Studies of dose-dependent effects of transresveratrol showed antiproliferative activity with an EC50 value of 78.9 +/- 5.4 mu M. Caspase-3 was activated in a dose-dependent manner after incubation for 24 h giving an EC50 value of 276.1 +/- 1.7 mu M. Apoptosis was also confirmed with microscopic observation of changes in membrane permeability and detection of DNA fragmentation. The activity of trans-resveratrol on the mitochondria apoptosis pathway was evidenced by the production of superoxide anions in the mitochondria of cells undergoing apoptosis. In conclusion, trans-resveratrol inhibits cell proliferation without cytotoxicity and induces apoptosis in HT-29. Results of the present study provide evidence demonstrating the antitumor effect of trans-resveratrol via a ROS-dependent apoptosis pathway in colorectal carcinoma.