Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
Department of Liver Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 17# 3rd Section, R en Min South Road, 610041 Chengdu, China.
Biomed Pharmacother. 2017 Sep;93:976-984. doi: 10.1016/j.biopha.2017.07.008. Epub 2017 Jul 14.
Prostate cancer is a big threat to male for its poor prognosis and high mortality rate. Natural compounds are important resources of many anticancer drugs. Pomegranate is a kind of antioxidant-rich fruit and its peel and seed has potential anticancer activities. In this study, we aimed to investigate the effects of pomegranate peel extract (PoPx) on the apoptosis and metastasis of prostate cancer cells and the related mechanism. We found that PoPx showed growth inhibition on prostate cancer cells. Nuclei morphological and flow cytometer (FCM) analysis indicated that PoPx could induce prostate cancer apoptosis. Further investigation indicated that mitochondrial mediated intrinsic pathway is involved in the apoptosis. Exposure to PoPx led to loss of mitochondrial transmembrane potential (Δym), accumulation of reactive oxygen species (ROS). Western blot analysis showed that PoPx could increase the expression ratio of Bax/Bcl2 and activation of apoptosis executor caspase 3. Wound healing assay and transwell migration and invasion assay implied that PoPx has the potential to inhibit migration and invasion, two critical steps in prostate cancer metastasis. Downregulation of MMP2/MMP9 and upregulation of TIMP2 showed accordance with the inhibition of migration and invasion. In summary, the present data showed that PoPx could be a promising drug candidate to treat prostate cancer, showing us a better way to develop novel drugs from natural compounds.
前列腺癌因其预后不良和高死亡率对男性构成巨大威胁。天然化合物是许多抗癌药物的重要资源。石榴是一种富含抗氧化剂的水果,其果皮和种子具有潜在的抗癌活性。在这项研究中,我们旨在研究石榴皮提取物(PoPx)对前列腺癌细胞凋亡和转移的影响及其相关机制。我们发现 PoPx 对前列腺癌细胞的生长具有抑制作用。细胞核形态学和流式细胞仪(FCM)分析表明,PoPx 可以诱导前列腺癌细胞凋亡。进一步的研究表明,线粒体介导的内在途径参与了凋亡。暴露于 PoPx 会导致线粒体跨膜电位(Δym)丧失和活性氧(ROS)积累。Western blot 分析表明,PoPx 可以增加 Bax/Bcl2 的表达比值,并激活凋亡执行器 caspase 3。伤口愈合试验、Transwell 迁移和侵袭试验表明,PoPx 具有抑制迁移和侵袭的潜力,而迁移和侵袭是前列腺癌转移的两个关键步骤。MMP2/MMP9 的下调和 TIMP2 的上调与迁移和侵袭的抑制一致。总之,本研究数据表明,PoPx 可能是治疗前列腺癌的一种有前途的药物候选物,为我们从天然化合物中开发新型药物提供了更好的途径。