Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

作     者：FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni 

作者机构：Department of Public HealthGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Department of Pediatric CardiologyHeart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China Department of Basic Medical SciencesCollege of MedicineUniversity of SharjahSharjah 57545United Arab Emirates Department of RadiologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research CenterFukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan Department of Environmental HealthSchool of Medical SciencesUniversity of FukuiFukui 910-8580Japan 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2024年第22卷第5期

页      面：387-401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] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：This work was supported by JSPS KAKENHI(Nos.20K10449 and 23K09645) 

主　　题：Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy 

摘      要：Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st