Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption
Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption
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DOI：
10.21873/anticanres.11168
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发表时间：
2016-11-01
影响因子：
2
通讯作者：
Ahn, Soon-Cheol
中科院分区：
文献类型：
--
作者：
Kim, Sang-Hun;Kim, Kwang-Youn;Ahn, Soon-Cheol
背景：莫能菌素是一种羧基聚醚离子载体，能有效抑制多种癌细胞的生长。最近，莫能菌素的抗癌作用已被公认的基础上，其诱导癌细胞凋亡的能力。然而，莫能菌素的抗癌作用及其作用机制还有待研究，特别是对人前列腺癌细胞。材料与方法：检测细胞活力、蛋白质印迹法、细胞周期阻滞、膜联蛋白V/碘化丙啶法、活性氧（ROS）产生和细胞内Ca ~（2+）通量。结果：在这项研究中，莫能菌素显着抑制前列腺细胞系中的细胞活力以剂量依赖性的方式。此外，莫能菌素对PC-3细胞生长的抑制通过调节细胞周期和凋亡相关蛋白诱导细胞周期停滞和细胞凋亡。此外，莫能菌素诱导ROS的产生和Ca 2+稳态的破坏，这是恢复的二苯基碘，线粒体ROS抑制剂和维拉帕米，Ca 2+通道阻滞剂，分别证实了前半胱天冬酶-3激活和聚ADP核糖聚合酶切割。结论：莫能菌素通过调节细胞周期和凋亡相关蛋白诱导细胞周期停滞和凋亡，分别导致诱导线粒体ROS和Ca 2+依赖性凋亡。
Background: Monensin is a carboxyl polyether ionophore that potently inhibits the growth of various cancer cells. Recently, the anticancer effects of monensin have been recognized based on its ability to induce apoptosis in cancer cells. However, anticancer effect of monensin and its mechanism of action have yet to be investigated, especially against human prostate cancer cells. Materials and Methods: Cell viability assay, western blot, cell-cycle arrest, annexin V/propidium iodide assay, reactive oxygen species (ROS) production and intracellular Ca2+ flux were assayed. Results: In this study, monensin significantly inhibited cell viability in a dose-dependent manner in prostate cell lines. Moreover, cell growth inhibition by monensin induced G(1) phase cell-cycle arrest and apoptosis via regulation of cell cycle-and apoptosis-related proteins in PC-3 cells. In addition, monensin induced the production of ROS and the disruption of Ca2+ homeostasis, that was restored by diphenyleneiodonium, a mitochondrial ROS inhibitor and verapamil, a Ca2+ channel blocker, respectively, as confirmed by pro-caspase-3 activation and poly ADP ribose polymerase cleavage. Conclusion: Monensin induces cell-cycle arrest and apoptosis through regulation of cell cycle-and apoptosis-related proteins, resulting in induction of mitochondrial ROS-and Ca2+-dependent apoptosis, respectively.