Resveratrol protects cardiomyocytes from doxorubicin-induced apoptosis through the AMPK/P53 pathway

被引:64
作者
Liu, Mi-Hua [1 ]
Lin, Xiao-Long [2 ]
Guo, Dong-Ming [3 ]
Zhang, Yuan [4 ]
Yuan, Cong [5 ]
Tan, Tian-Ping [1 ]
Chen, Yu-Dan [1 ]
Wu, Shao-Jian [1 ]
Ye, Zu-Feng [1 ]
He, Jun [1 ]
机构
[1] Univ South China, Affiliated Nanhua Hosp, Dept Clin Lab, 336 Dongfeng South Rd, Hengyang 421001, Hunan, Peoples R China
[2] Guangzhou Med Univ, Peoples Hosp Huizhou 3, Dept Pathol, Huizhou 516002, Guangdong, Peoples R China
[3] Univ South China, Lab Clin Anat, Hengyang 421001, Hunan, Peoples R China
[4] Mawangdui Hosp, Dept Pathol, Changsha 410016, Hunan, Peoples R China
[5] First Hosp Changsha, Dept Cardiol, Changsha 410005, Hunan, Peoples R China
关键词
resveratrol; doxorubicin; apoptosis; P53; adenosine monophosphate-activated protein kinase; INDUCED CARDIOTOXICITY; CELL-DEATH; PC12; CELLS; KINASE; INHIBITION; ACTIVATION; STRESS; ALPHA; P53;
D O I
10.3892/mmr.2015.4665
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 mu M DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration amplified P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX-induced apoptosis via the AMPK/P53 pathway.
引用
收藏
页码:1281 / 1286
页数:6
相关论文
共 25 条
[1]
Hydrogen peroxide inhibits mTOR signaling by activation of AMPKα leading to apoptosis of neuronal cells [J].
Chen, Long ;
Xu, Baoshan ;
Liu, Lei ;
Luo, Yan ;
Yin, Jun ;
Zhou, Hongyu ;
Chen, Wenxing ;
Shen, Tao ;
Han, Xiuzhen ;
Huang, Shile .
LABORATORY INVESTIGATION, 2010, 90 (05) :762-773
[2]
Activation of AMP-Activated Protein Kinase Contributes to Doxorubicin-Induced Cell Death and Apoptosis in Cultured Myocardial H9c2 Cells [J].
Chen, Min-Bin ;
Wu, Xiao-Yang ;
Gu, Jin-Hua ;
Guo, Qing-Tao ;
Shen, Wen-Xiang ;
Lu, Pei-Hua .
CELL BIOCHEMISTRY AND BIOPHYSICS, 2011, 60 (03) :311-322
[3]
Resveratrol and red wine, healthy heart and longevity (vol 15, pg 467, 2010) [J].
Das, Dipak K. ;
Mukherjee, Subhendu ;
Ray, Diptarka .
HEART FAILURE REVIEWS, 2011, 16 (04) :425-435
[4]
Das S, 2006, ARZNEIMITTEL-FORSCH, V56, P700
[5]
Resveratrol, a polyphenol phytoalexin, protects against doxorubicin-induced cardiotoxicity [J].
Gu, Jun ;
Hu, Wei ;
Zhang, Da-dong .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2015, 19 (10) :2324-2328
[6]
Exogenous Hydrogen Sulfide Protects against Doxorubicin-Induced Inflammation and Cytotoxicity by Inhibiting p38MAPK/NFκB Pathway in H9c2 Cardiac Cells [J].
Guo, Runmin ;
Wu, Keng ;
Chen, Jingfu ;
Mo, Liqiu ;
Hua, Xiaoxiao ;
Zheng, Dongdan ;
Chen, Peixi ;
Chen, Gang ;
Xu, Wenming ;
Feng, Jianqiang .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (06) :1668-1680
[7]
Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells [J].
Guo, Runmin ;
Lin, Jiancong ;
Xu, Wenming ;
Shen, Ning ;
Mo, Liqiu ;
Zhang, Changran ;
Feng, Jianqiang .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2013, 31 (03) :644-650
[8]
AMP-activated protein kinase induces a p53-dependent metabolic checkpoint [J].
Jones, RG ;
Plas, DR ;
Kubek, S ;
Buzzai, M ;
Mu, J ;
Xu, Y ;
Birnbaum, MJ ;
Thompson, CB .
MOLECULAR CELL, 2005, 18 (03) :283-293
[9]
Anthracycline-related cardiotoxicity in childhood cancer survivors [J].
Lipshultz, Steven E. ;
Karnik, Ruchika ;
Sambatakos, Peter ;
Franco, Vivian I. ;
Ross, Samuel W. ;
Miller, Tracie L. .
CURRENT OPINION IN CARDIOLOGY, 2014, 29 (01) :103-112
[10]
ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes [J].
Liu, Jiahao ;
Mao, Weike ;
Ding, Bo ;
Liang, Chang-Seng .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 295 (05) :H1956-H1965