title: Activation of AMP-activated protein kinase contributes to doxorubicin-induced cell death and apoptosis in cultured myocardial H9c2 cells.
abstract: Despite its potent antitumor effect, clinical use of Doxorubicin is limited because of serious side effects including myocardial toxicity. Understanding the cellular mechanism involved in this process in a better manner is beneficial for optimizing Doxorubicin treatment. In the current study, the authors focus on the AMP-activated protein kinase (AMPK) in the said process. In this study, the authors discovered for the first time that Doxorubicin induces AMPK activation in cultured rat embryonic ventricular myocardial H9c2 cells. Reactive oxygen species (ROS)-dependent LKB1 activation serves as the upstream signal for AMPK activation by Doxorubicin. Evidence in support of the activation of AMPK contributing to Doxorubicin-induced H9c2 cell death/apoptosis--probably by modulating multiple downstream signal targets, including regulating JNK, p53, and inhibiting mTORC1--is provided in this article.
authors.affiliation: Department of Medical Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, 91 Qianjin Road, Kunshan 215300, Jiangsu Province, China. cmb1981@163.com.cn
authors.forename: Min-Bin
authors.initials: MB
authors.lastname: Chen
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Wu
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Gu
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Guo
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Shen
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Lu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004317:Doxorubicin / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases