AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer

作     者：Yi LI Wenyan SHE Xiaoran XU Yixin LIU Xinyu WANG Sheng TIAN Shiyi LI Miao WANG Chaochao YU Pan LIU Tianhe HUANG Yongchang WEI Yi LI;Wenyan SHE;Xiaoran XU;Yixin LIU;Xinyu WANG;Sheng TIAN;Shiyi LI;Miao WANG;Chaochao YU;Pan LIU;Tianhe HUANG;Yongchang WEI

作者机构：Department of Radiation and Medical OncologyZhongnan Hospital of Wuhan UniversityHubei Cancer Clinical Study Center&Hubei Key Laboratory of Tumor Biological BehaviorsWuhan 430071China College of Chemistry and Molecular ScienceWuhan UniversityWuhan 430071China Department of Integrated Chinese and Western MedicineZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2023年第24卷第3期

页      面：232-247页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Wuhan University Zhongnan Hospital Translational Medicine and Interdisciplinary Research Joint Fund(No.ZNJC201910) China 

主　　题：N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2) Gastric cancer Reactive oxygen species(ROS) Apoptosis Pyruvate dehydrogenase kinase 1(PDK1) Glucose metabolism 

摘      要：Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ***,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer(GC).Mechanistically,by targeting pyruvate dehydrogenase kinase 1(PDK1),AAZ2 caused metabolism alteration and the imbalance of redox homeostasis,followed by the inhibition of phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway and leading to the activation of B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)/caspase-9(Cas9)/Cas3 ***,our in vivo data demonstrated that AAZ2 could inhibit the growth of GC ***,our data suggested that AAZ2 could contribute to metabolic abnormalities,leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.