Mechanisms of resveratrol-induced changes in [Ca2+]i and cell viability in PC3 human prostate cancer cells
Mechanisms of resveratrol-induced changes in [Ca2+]i and cell viability in PC3 human prostate cancer cells
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DOI：
10.3109/10799893.2013.822886
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Jan, Chung-Ren
中科院分区：
文献类型：
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作者：
Chang, Hong-Tai;Chou, Chiang-Ting;Jan, Chung-Ren
白藜芦醇是一种天然化合物，可影响不同细胞中的细胞Ca 2+稳态和活力。本研究检测了白藜芦醇对PC 3人前列腺癌细胞胞浆游离Ca 2+浓度（[Ca 2 +]（i））和活力的影响。Ca 2+敏感性荧光染料fura-2用于测量[Ca 2 +]（i），WST-1用于测量活力。白藜芦醇诱发的[Ca 2 +]（i）浓度依赖性升高。通过去除细胞外Ca 2+降低反应。硝苯地平、益康唑、SKF 96365和蛋白激酶C抑制剂GF 109203 X不能抑制白藜芦醇诱导的钙内流，但蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13乙酸酯几乎可以消除白藜芦醇诱导的钙内流。在无钙培养基中，内质网钙泵抑制剂2，5-二叔丁基对苯二酚可降低白藜芦醇引起的[Ca 2 +]（i）升高。相反，白藜芦醇治疗抑制BHQ诱发的[Ca 2 +]（i）升高。用U 73122抑制磷脂酶C不会改变白藜芦醇诱发的[Ca 2 +]升高（i）。以前的研究表明，白藜芦醇在10和100 μ M之间诱导包括PC 3细胞在内的各种癌细胞类型的细胞死亡。然而，在这项研究中，白藜芦醇（1-10 μ M）增加细胞活力，这是取消螯合胞质Ca 2+与1，2-双（2-氨基苯氧基）乙烷-N，N，N '，N'-四乙酸-乙酰氧基甲酯（BAPTA/AM）。因此，它表明，在PC 3细胞，白藜芦醇有一个双重的影响，对生存能力：在低浓度（1-10 μ M），它诱导增殖，而在较高浓度时，它导致细胞死亡。总的来说，我们的数据表明，在PC 3细胞中，白藜芦醇通过蛋白激酶C调节的机制，引起磷脂酶C非依赖性的Ca 2+从内质网释放和Ca 2+进入，从而诱导[Ca 2 +]（i）升高。1-10 μ M的白藜芦醇也引起Ca ~（2+）依赖性细胞增殖。
Resveratrol is a natural compound that affects cellular Ca2+ homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca2+ concentrations ([Ca2+](i)) and viability in PC3 human prostate cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+](i) and WST-1 was used to measure viability. Resveratrol-evoked [Ca2+](i) rises concentration-dependently. The response was reduced by removing extracellular Ca2+. Resveratrol-evoked Ca2+ entry was not inhibited by nifedipine, econazole, SKF96365 and the protein kinase C inhibitor GF109203X, but was nearly abolished by the protein kinase C activator phorbol 12-myristate 13 acetate. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone decreased resveratrol-evoked rise in [Ca2+](i). Conversely, treatment with resveratrol inhibited BHQ-evoked rise in [Ca2+](i). Inhibition of phospholipase C with U73122 did not alter resveratrol-evoked rise in [Ca2+](i). Previous studies showed that resveratrol between 10 and 100 mu M induced cell death in various cancer cell types including PC3 cells. However, in this study, resveratrol (1-10 mu M) increased cell viability, which was abolished by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid-acetoxymethyl ester (BAPTA/AM). Therefore, it is suggested that in PC3 cells, resveratrol had a dual effect on viability: at low concentrations (1-10 mu M) it induced proliferation, whereas at higher concentrations it caused cell death. Collectively, our data suggest that in PC3 cells, resveratrol-induced rise in [Ca2+](i) by evoking phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry, via protein kinase C-regulated mechanisms. Resveratrol at 1-10 mu M also caused Ca2+ dependent cell proliferation.