Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple

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Resveratrol,a natural compound extracted from the skins of grapes,berries,or other fruits,has been shown to have anti-tumor effects against multiple myeloma(MM)via promoting apopto-sis and inhibiting cell viability.In addition to apoptosis,autophagy also plays a significant role in anti-tumor effects.However,whether autophagy is involved in anti-MM activity of resvera-trol remains unclear.In this study,human MM cell lines U266,RPMI-8226,and NCI-H929 were treated with resveratrol.Cell Counting Kit-8 assay and colony formation assay were used to mea-sure cell viability.Western blot analysis was used to detect apoptosis-and autophagy-associated proteins.3-Methyladenine(3-MA)was applied to inhibit autophagy.Results showed that resvera-trol inhibited cell viability and colony formation via promoting apoptosis and autophagy in MM cell lines U266,RPMI-8226,and NCI-H929.Resveratrol promoted apoptosis-related proteins,Caspase-3 activating poly-ADP-ribose polymerase and Caspase-3 cleavage,and decreased the protein level of Survivin in a dose-dependent manner.Additionally,resveratrol upregulated the levels of LC3 and Beclin1 in a dose-dependent way,indicating that autophagy might be implicated in anti-MM effect of resveratrol.Furthermore,3-MA relieved the cytotoxicity of resveratrol by blocking the autophagic flux.Resveratrol increased the phosphorylation of adenosine monophosphate(AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin(mTOR)and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner,lead-ing to autophagy.Therefore,our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy,which can be used as a new therapeutic strategy for MM in clinic.
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