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

查看全文 作　　者：Ruye [1]Ma;Dandan [1]Yu;Yu [1]Peng;Hongfei [1]Yi;Yingcong [1]Wang;Taofang [1]Cheng;Bingqing [1]Shi;Guang [1]Yang;Weiming [1]Lai;Xiaosong [1]Wu;Ye [2]Lu;Jumei [1]Shi

机构地区：[1]Department of Hematology,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Shanghai 200072,China;[2]Department of Hematology and Oncology,Soochow University Affiliated Taicang Hospital(the First Peoples Hospital of Taicang),Taicang 215400,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2021年第53卷第6期,共9页

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81670194,81870158,81900210,and 81900211)。 摘　　要：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 apoptosis 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 resveratrol 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 measure 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 resveratrol 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,leading 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. 关键词：multiple myeloma RESVERATROL AUTOPHAGY APOPTOSIS AMP-activated protein kinase

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

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