Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells
Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells
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DOI：
10.1074/jbc.m114.583575
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发表时间：
2014-12-19
影响因子：
4.8
通讯作者：
Boehning, Darren
中科院分区：
文献类型：
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作者：
Borahay, Mostafa A.;Kilic, Gokhan S.;Boehning, Darren
他汀类药物通常用于治疗高血浆胆固醇水平。除了这些众所周知的降脂特性外，它们在体内还具有广泛的作用，包括抗肿瘤作用。他汀类药物可抑制多种肿瘤的生长。然而，这些机制仍然不完全清楚。在这里，我们显示辛伐他汀抑制人子宫肌瘤细胞的增殖。这与丝裂原活化蛋白激酶信号的减少和细胞周期进程的多重变化有关。辛伐他汀能有效地刺激子宫肌瘤细胞的凋亡，其机制依赖于电压门控钙通道的钙离子释放。因此，辛伐他汀具有抗肿瘤作用，其作用依赖于细胞凋亡的钙释放机制。
Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.