Abstract
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering’.
Highlights
Statins potently inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme
Basic research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies [16]
In several phase II or III randomized clinical trials (RCTs), lovastatin with ubiquinone was ineffective for patients with advanced gastric adenocarcinoma [127], epirubicin, cisplatin, and capecitabine plus pravastatin did not improve progression-free survival (PFS) at six months compared with the chemotherapy alone [128], and capecitabine and cisplatin plus simvastatin did not increase
Summary
Statins potently inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. The development of statins as cholesterol-lowering agents began in the mid-1970s when they were discovered as a fungal metabolite, with the first of these being a natural product called mevastatin [1]. Since this discovery, vigorous efforts have been made to develop novel statins, leading to the introduction of a total of eight varieties to date. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; the effects of statins on cancer patients have not yet been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer, in addition to the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering’
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