Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Molecular Medicine Reports
Yuan-Yuan ShenYue-Yin Pan

Abstract

Breast carcinoma is the leading cause of cancer-associated mortality in female individuals worldwide. Previous studies have investigated the pro-apoptotic and antimetastatic effects of statins, and have demonstrated that simvastatin exhibits antitumor activity and potent chemopreventive effects. However, the mechanism underlying the effects of simvastatin in breast cancer remains to be elucidated. The present study demonstrated that simvastatin inhibited the proliferation of MDA-MB-231 human breast cancer cells in a dose-dependent manner, decreased the protein expression of B cell lymphoma 2 (Bcl-2) and increased the protein expression of Bcl-2-associated X protein in time- and dose-dependent manners. In addition, simvastatin arrested cells in the G0/G1 phase of the cell cycle, downregulated the protein expression levels of cyclin D1 and cyclin-dependent kinase (CDK)2, mediated the mitochondria-dependent caspase cascade by increasing the protein expression levels of caspase-3, -8 and -9, and downregulated the protein expression of X-linked inhibitor of apoptosis, which induced cell apoptosis. In addition, simvastatin decreased the protein expression of matrix metalloproteinase (MMP)-2 and suppressed the activation of nuclear fa...Continue Reading

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Citations

Aug 19, 2020·Drug Development and Industrial Pharmacy·Iman AkbarzadehHaleh Bakhshandeh
Nov 9, 2017·International Journal of Oncology·Ji Young LeeYoun Kyoung Jeong
Mar 1, 2019·International Journal of Molecular Sciences·Kamila Środa-PomianekOlga Wesołowska
Apr 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Charleston F ChristieEduardo N Maldonado
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Anna Palko-ŁabuzKrystyna Michalak

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