The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells

The ability of lovastatin, mevastatin and simvastatin to inhibit the melanoma cell proliferation was examined using cytotoxicity and apoptosis assays. Effects on cell migration and invasion were assessed using transwell invasion and migration chambers. Hypothesis testing was performed using 1-way ANOVA, and Student's t-test.Lovastatin, mevastatin and simvastatin inhibited the growth, cell migration and invasion of HT144, M14 and SK-MEL-28 melanoma cells. The concentrations required to inhibit proliferation of melanoma cells (0.8–2.1 μM) have previously been achieved in a phase I clinical trial of lovastatin in patients with solid tumours, (45 mg/kg/day resulted in peak plasma concentrations of approximately 3.9 μM).Our results suggest that statin treatment is unlikely to prevent melanoma development at standard doses. However, higher doses of statins may have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells.The statins are group of drugs routinely used in the treatment of lipid disorders, including hypercholesterolemia. Statins exert their effects through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). HMG-CoA reductase catalyses the conversion of HMG-CoA into mevalonate in the mevalonate biosynthetic pathway [1,2].In addition to the cholesterol lowering effects of statins, a number of recent studies suggest that the cancer incidence rates may be lower in patients receiving statins. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trial to evaluate the efficacy of lovastatin for preventing coronary events, found a significantly decreased incidence of new melanomas in the lovastatin arm compared with the placebo arm. In addition, among the 41 participants who developed melanoma, there was a trend, although not statistically significant, toward earlier stage at diagnosis in the lovastatin group [3]. A recent meta-analysis described the incidence of melanoma in 12