Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway

作     者：Shanshan Qi Lingyuan Guo Shuzhen Yan Robert J.Lee Shuqin Yu Shuanglin Chen 

作者机构：Jiangsu Province Key Laboratory for Microbes and Functional Genomics College of Life SciencesNanjing Normal University College of Pharmacy the Ohio State University Cancer Pharmacology Crown Bioscience Inc. Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life SciencesNanjing Normal University 

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

年 卷 期：2019年第9卷第2期

页      面：279-293页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Project No.81673214) The National Key Technology Research and National Key Technology Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(Project No.2012BAD36B0502) the Priority Academic Program Development of Jiangsu Higher Educational Institutions(China) 

主　　题：Hypocrellin A Photodynamic therapy Reactive oxygen species Proteomic LC–MS/MS iTRAQ 

摘      要：Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy(PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation(iTRAQ) 2 D liquid chromatography with tandem mass spectrometric(LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspaseinhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation,and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species(ROS) generations. Further studies showed that PDT treatment with 0.08 mmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3,-9, ***, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.