Resveratrol Induces Apoptosis and Autophagy in T-cell Acute Lymphoblastic Leukemia Cells by Inhibiting Akt/mTOR and Activating p38-MAPK

查看全文 作　　者：GE [1]Jiao;LIU [1]Yan;LI [1]Qiang;GUO [1]Xia;GU [1]Ling;MA Zhi [1]Gui;ZHU Yi [1]Ping

机构地区：[1]Department of Pediatric Hematology/Oncology,West China Second University Hospital,Sichuan University

出　　处：《Biomedical and Environmental Sciences》索引2013年第26卷第11期,共10页

基　　金：supported by grants from the Department of Science and Technology of Sichuan Province,China (No.2008JY0029-1 and No.07FG002-024);research funds from the Program for Changjiang Scholars and Innovative-Research Team in University (No.IRT0935) 摘　　要：Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia(T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase(CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins(Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins(Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced.Conclusion Our findings have suggested that resveratrol induces cell cycle arrest,apoptosis,and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways.Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol.Therefore,the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL. 关键词：细胞周期蛋白依赖性激酶淋巴细胞白血病白血病细胞白藜芦醇细胞凋亡 mTOR Akt 诱导

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Resveratrol Induces Apoptosis and Autophagy in T-cell Acute Lymphoblastic Leukemia Cells by Inhibiting Akt/mTOR and Activating p38-MAPK

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