Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9

Background and Objectives. Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Despite several advances in therapeutic options, the disease remains incurable. Recently, it was repeatedly demonstrated that statins, competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have antineoplastic effects. Therefore we aimed to study the effects of simvastatin (Sim) on malignant B cells derived from patients with CLL and mechanisms of action of the drug. Methods and Results. Purified B-CLL cells from 15 patients were cultured either alone or with Sim at concentrations of 10, 50, and 100 μM. Viability, measured by the activity of mitochondrial dehydrogenases, was reduced significantly in the cells treated with Sim at 50 and 100 μM for 24 hours ( p