Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

Abstract

Background: Recently, cytotoxic effects of statins on breastcancer cells have been reported. However, the mechanism of antiproliferativeeffects is currently unknown. Autophagy is non-apoptoticprogrammed cell death, which is characterized by degradation ofcytoplasmic components and as having a role in cancer pathogenesis.Aims: To investigate the anti-proliferative effects of atorvastatinon MCF-7 human breast adenocarcinoma cells with respect to bothautophagy and apoptosis.Study Design: Cell culture study.Methods: Cell viability was analyzed using WST-1 cell proliferationassay. Apoptosis was determined by the TUNEL method, whereasautophagy was assessed by Beclin-1 and LC3B immunofluorescencestaining. Ultrastructural analysis of cells was performed by electronmicroscopy.Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- andtime-dependent manner inducing TUNEL-, Beclin-1-, and LC3Bpositivecells. Moreover, ultrastructural analysis showed apoptotic,autophagic, and necrotic morphological changes in treatment groups.A statistically significant increase in the apoptotic index was detectedwith higher concentrations of atorvastatin at 24 h and 48 h (p