Statin-Induced Inhibition of MCF-7 Breast Cancer Cell Proliferation is Related to Cell Cycle Arrest and Apoptotic and Necrotic Cell Death Mediated by an Enhanced Oxidative Stress

Abstract

Statins have antiproliferative and anti-tumoral effects in MCF-7 cells. We determined the effect of statins upon MCF-7 cell cycle, toxicity, cell death, reactive oxygen species (ROS) production and mitochondrial membrane potential. Fluvastatin, simvastatin and atorvastatin inhibited cell proliferation. Antiproliferation was associated with a decrease in the DNA synthesis and a cell cycle arrest in the G1 and G2/M phases. A loss in the mitochondrial membrane potential was observed with fluvastatin. Statins induced increase in ROS production that was associated with cell death, which was abrogated by the antioxidant NAC. Our results suggest that the cytotoxic effect observed is mediated by an oxidative stress.

Keywords:

• Statins
• Cell cycle
• Cell death
• Oxidative stress
• MCF-7

ABBREVIATIONS
DCFDA	=	2,7-dichlorofluorescein diacetate
HMG-CoA	=	3-hydroxyl-3-methylglutaralyl-coenzyme A
MTT	=	3-(4,5-dimethylthiazoil-2-yl)-2,5-diphenyltentrazolium bromide
NAC	=	N-acetyl-L-cysteine
PI	=	propidium iodide
Rh123	=	rhodamine 123
ROS	=	reactive oxygen species

ABBREVIATIONS
DCFDA	=	2,7-dichlorofluorescein diacetate
HMG-CoA	=	3-hydroxyl-3-methylglutaralyl-coenzyme A
MTT	=	3-(4,5-dimethylthiazoil-2-yl)-2,5-diphenyltentrazolium bromide
NAC	=	N-acetyl-L-cysteine
PI	=	propidium iodide
Rh123	=	rhodamine 123
ROS	=	reactive oxygen species