Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation
Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation
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DOI：
10.1016/j.taap.2007.12.027
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发表时间：
2008-05-15
影响因子：
3.8
通讯作者：
Katiyar, Santosh K.
中科院分区：
文献类型：
--
作者：
Meeran, Syed M.;Katiyar, Suchitra;Katiyar, Santosh K.
植物化学物质显示出作为潜在的化学预防剂或化学治疗剂对各种癌症的承诺。在这里，我们报告了小檗碱，一种植物化学物质，对人前列腺癌细胞的化疗作用。小檗碱处理人前列腺癌细胞（PC-3）诱导剂量依赖性凋亡，但这种作用的小檗碱在非肿瘤性人前列腺上皮细胞（PWR-IE）中没有看到。小檗碱诱导的细胞凋亡与线粒体膜电位的破坏，从线粒体释放促凋亡分子（细胞色素c和Smac/DIABLO）和caspase-9，-3和PARP蛋白的裂解有关。黄连素对前列腺癌细胞的这种作用是由活性氧（ROS）的产生启动的，而与雄激素的反应无关，ROS的产生是通过增加黄嘌呤氧化酶的诱导。用别嘌呤醇（黄嘌呤氧化酶抑制剂）处理细胞，可抑制小檗碱诱导的癌细胞氧化应激。小檗碱诱导的细胞凋亡被阻断的存在下，抗氧化剂，N-乙酰半胱氨酸，通过防止破坏线粒体膜电位和随后释放的细胞色素c和Smac/DIABLO。综上所述，本研究揭示了小檗碱介导的人前列腺癌细胞死亡是由活性氧调节的，因此表明小檗碱可能被认为是一种有前途的前列腺癌治疗候选药物。(C)2008年爱思唯尔公司All rights reserved.
Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-IE). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer. (C) 2008 Elsevier Inc. All rights reserved.