HMG-CoA reductase inhibitor(Pravastatin) inhibits endothelial cell proliferation dependent on cell cycle arrest Free

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HMG-CoA reductase inhibitors, namely statins, have been developed as lipid-lowering drugs and are well recognized to reduce morbidity and mortality from coronary artery disease. In addition to the conventional anti-lipid effect, several recent experimental studies have focused on the anti-tumor effects of statins, and have shown that they inhibited the proliferation of tumor cells in vitro and reduced liver metastasis of pancreatic cancer in vivo. In the present study, we aimed to investigate the potential anti-angiogenic effect of pravastatin, and for this purpose we used a model of tumor angiogenesis consisting of human umbilical vein endothelial cells (HUVECs). Pravastatin, kindly gifted by Sankyo Co., Ltd., dose-dependently inhibited the proliferative activity of HUVECs. This inhibitory effect was dependent on the induction of cell cycle arrest to the G1 phase, but not on cell apoptosis. Pravastatin treatment caused a decrease in the expression of cyclin-D, -E and cyclin-dependent kinase (CDK)-2, which are important regulators of cell cycle transition from G1 to S phase. In addition, high-dose Pravastatin also caused inhibition of capillary-like tubular formation, an important step of angiogenesis, by HUVECs. Angiogenesis is essential for tumor development and progression, and consequently, inhibition of angiogenesis may be an attractive strategy for the treatment of cancer. Here, we could clearly demonstrate that Pravastatin inhibited endothelial cell proliferation and capillary-like tube formation, which are two essential steps for angiogenesis to occur, and consequently, the potential applicability of Pravastatin as an anticancer drug is suggested.