Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro
Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro
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DOI：
10.1016/j.biopha.2016.03.023
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发表时间：
2016-05-01
影响因子：
7.5
通讯作者：
Yin, Wenya
中科院分区：
文献类型：
--
作者：
Li, Yali;Yang, Fangfang;Yin, Wenya
大多数非小细胞肺癌的常规治疗都伴随着严重的副作用，并且这种癌症的发病率和死亡率在全球范围内迅速增加。本研究旨在探讨石榴叶提取物（PLE）对非小细胞肺癌细胞系A549、H1299和小鼠Lewis肺癌细胞系LL/2的体外抗癌作用，并探讨其作用机制。我们的结果表明，PLE 以浓度和时间依赖性方式抑制非小细胞肺癌细胞系的细胞增殖。流式细胞术 (FCM) 检测显示，PLE 通过以剂量依赖性方式将细胞周期进程阻滞在 G2/M 期并诱导细胞凋亡来影响 H1299 细胞的存活。此外，PLE还可以降低活性氧（ROS）和线粒体膜电位（Delta Ym），表明PLE可能通过线粒体介导的凋亡途径诱导细胞凋亡。此外，PLE 阻断 H1299 细胞迁移和侵袭，体外还观察到基质金属蛋白酶 (MMP)、MMP-2 和 MMP-9 表达减少。这些结果表明，PLE 通过抑制增殖、诱导细胞凋亡、细胞周期阻滞和损害细胞迁移和侵袭，可能成为非小细胞肺癌治疗中有效且安全的化疗药物。 (C) 2016 Elsevier Masson SAS。版权所有。
Most conventional treatments on non-small cell lung carcinoma always accompany with awful side effects, and the incidence and mortality rates of this cancer are increasing rapidly worldwide. The objective of this study was to examine the anticancer effects of extract of Punica granatum (pomegranate) leaves extract (PLE) on the non-small cell lung carcinoma cell line A549, H1299 and mouse Lewis lung carcinoma cell line LL/2 in vitro, and explore its mechanisms of action. Our results have shown that PLE inhibited cell proliferation in non-small cell lung carcinoma cell line in a concentration-and time-dependent manner. Flow cytometry (FCM) assay showed that PLE affected H1299 cell survival by arresting cell cycle progression in G2/M phase in a dose-dependent manner and inducing apoptosis. Moreover, PLE could also decrease the reactive oxygen species (ROS) and the mitochondrial membrane potential (Delta Ym), indicating that PLE may induce apoptosis via mitochondria-mediated apoptotic pathway. Furthermore, PLE blocked H1299 cell migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. These results suggested that PLE could be an effective and safe chemotherapeutic agent in non-small cell lung carcinoma treatment by inhibiting proliferation, inducing apoptosis, cell cycle arrest and impairing cell migration and invasion. (C) 2016 Elsevier Masson SAS. All rights reserved.