Raloxifene induces autophagy-dependent cell death in breast cancer cells via the activation of AMP-activated protein kinase.

摘要: Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the (ER), and exhibits potent anti-tumor autophagy-inducing effects in breast cancer cells. However, mechanism of raloxifene-induced cell death autophagy not well-established. So, we analyzed underlying induced by raloxifene MCF-7 Treatment with significantly accumulated GFP-LC3 puncta increased level autophagic marker proteins, such as LC3-II, BECN1, ATG12-ATG5 conjugates, indicating activated autophagy. also flux indicators, cleavage GFP from only red fluorescence-positive mRFP-GFP-LC3-expressing An inhibitor, 3-methyladenine (3-MA), suppressed LC3-II blocked formation puncta. Moreover, siRNA targeting BECN1 markedly reversed raloxifene. Besides, was related caspases-7, -9, PARP. These results indicate activates autophagy-dependent but apoptosis. Interestingly, decreased intracellular adenosine triphosphate (ATP) AMPK/ULK1 pathway. However it AKT/mTOR Addition ATP phosphorylation AMPK well accumulation finally attenuating death. Our current study demonstrates induces via activation sensing decreases ATP, overactivation promotes thereby mediates anti-cancer