Cancer Management and Research (Jul 2019)
Statins induce cell apoptosis through a modulation of AKT/FOXO1 pathway in prostate cancer cells
Abstract
Jun-Li Deng,1,2 Rui Zhang,1,2 Ying Zeng,1,2 Yuan-Shan Zhu,3 Guo Wang1,21Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, People’s Republic of China; 3Department of Medicine, Weill Cornell Medicine, NY, NY 10065, USABackground: In recent years, statins have been frequently investigated in neoplasms. However, the potential roles of statins on prostate cancer cells and the underlying mechanisms have not been fully elucidated. In current study, we explored the effect and molecular mechanism of statins on cell proliferation and apoptosis in prostate cancer cells.Methods: Prostate cancer cell were treated with gradient doses of simvastatin and fluvastatin for 24–72 h. Cell proliferation was analyzed by using MTS assay and colony formation. Cell apoptosis was measured by Hoechst staining, flow cytometry and caspase-3 activity. Western blotting was used to evaluate the proteins levels.Results: Both simvastatin and fluvastatin produced a dose- and time-dependent inhibition of cell viability and colony formation while a promotion of cell apoptosis as evident with increases in caspase-3 activity, cleaved-caspase-3, cleaved-caspase-8 and cleaved-PARP levels in PC3 cells. Similar statin effects were observed in DU145 prostate cancer cells. Furthermore, statins produced a time- and dose-dependent reduction of phosphorylated-AKT and phosphorylated-FOXO1 levels in PC3 cells, and pretreatment of cells with an AKT phosphorylation inhibitor, MK2206, potentiated statins’ effect.Conclusion: Statins decrease cell proliferation and induce cell apoptosis, probably mediated via a downregulation of AKT/FOXO1 phosphorylation in prostate cancer cells, which may have a potential benefit in prostate cancer prevention and therapy.Keywords: statins, prostate cancer, apoptosis, AKT/FOXO1, pathway
