Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy

作     者：Yancheng Tang Liming Wang Tao Yi Jun Xu Jigang Wang Jiang-Jiang Qin Qilei Chen Ka-Man Yip Yihang Pan Peng Hong Yingying Lu Han-Ming Shen Hu-Biao Chen Yancheng Tang;Liming Wang;Tao Yi;Jun Xu;Jigang Wang;Jiang-Jiang Qin;Qilei Chen;Ka-Man Yip;Yihang Pan;Peng Hong;Yingying Lu;Han-Ming Shen;Hu-Biao Chen

作者机构：School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China School of Biomedical SciencesHunan UniversityChangsha 410082China Department of PhysiologyYong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Artemisinin Research CenterChina Academy of Chinese Medical SciencesBeijing 100700China The First Affiliated Hospital of Southern University of Science and Technologythe Second Clinical Medical College of Jinan UniversityShenzhen People’s HospitalShenzhen 518020China The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China epartment of Medical ResearchSeventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China Department of Biomedical ScienceCity University of Hong KongHong Kong SAR 999077China Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第12期

页      面：3966-3982页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by research grants from Innovation and Technology Fund(PRP/036/20FX,China) Health and Medical Research Fund(MHRF-16170251,China)of Hong Kong to Hu-Biao Chen Singapore Ministry of Education(MOE)Tier 2(MOE2018-T2-1-060,Singapore)to Han-Ming Shen National Natural Science Foundation of China(82074123 to Hu-Biao Chen,31501116 to Yingying Lu,82071441 to Liming Wang) 

主　　题：PINK1-Parkin-mediated mitophagy Magnolol Combination therapy Apoptosis Tumor suppression 

摘      要：Mitochondria as a signaling platform play crucial roles in deciding cell *** classic anticancer agents are known to trigger cell death through induction of mitochondrial ***,one selective autophagy,is the key mitochondrial quality control that effectively removes damaged ***,the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely ***,we examined the functional implication of mitophagy in the anticancer properties of magnolol,a natural product isolated from herbal Magnolia ***,we found that magnolol induces mitochondrial depolarization,causes excessive mitochondrial fragmentation,and increases mitochondrial reactive oxygen species(mtROS).Second,magnolol induces PTEN-induced putative kinase protein 1(PINK1)-Parkin-mediated mitophagy through regulating two positive feedforward amplification ***,magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis ***,magnolol prolongs the survival time of tumor-bearing ***,inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol s anticancer efficacy,both in vitro and in ***,our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis,whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol,suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.