Meeran Syed M, Katiyar Suchitra, Katiyar Santosh K
Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
Toxicol Appl Pharmacol. 2008 May 15;229(1):33-43. doi: 10.1016/j.taap.2007.12.027. Epub 2008 Jan 17.
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-1E). 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.
植物化学物质有望成为针对各种癌症的潜在化学预防或化学治疗剂。在此，我们报告一种植物化学物质黄连素对人前列腺癌细胞的化学治疗作用。用黄连素处理人前列腺癌细胞（PC-3）可诱导剂量依赖性凋亡，但在非肿瘤性人前列腺上皮细胞（PWR-1E）中未观察到黄连素的这种作用。黄连素诱导的凋亡与线粒体膜电位的破坏、凋亡分子（细胞色素c和Smac/DIABLO）从线粒体的释放以及半胱天冬酶-9、-3和PARP蛋白的切割有关。黄连素对前列腺癌细胞的这种作用是由活性氧（ROS）的产生引发的，与它们的雄激素反应性无关，并且ROS的产生是通过黄嘌呤氧化酶诱导的增加。用黄嘌呤氧化酶抑制剂别嘌呤醇处理细胞可抑制黄连素诱导的癌细胞氧化应激。在抗氧化剂N-乙酰半胱氨酸存在下，黄连素诱导的凋亡被阻断，这是通过防止线粒体膜电位的破坏以及随后细胞色素c和Smac/DIABLO的释放实现的。总之，本研究表明黄连素介导的人前列腺癌细胞死亡受活性氧调节，因此提示黄连素可能作为前列腺癌有前景的治疗候选物用于进一步研究。
