Original Articles
Shanshan Qi, Lingyuan Guo, Shuzhen Yan, Robert J. Lee, Shuqin Yu, Shuanglin Chen. Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway[J]. Acta Pharmaceutica Sinica B, 2019, 9(2): 279-293

Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway
Shanshan Qia,b, Lingyuan Guoa, Shuzhen Yana, Robert J. Leeb, Shuqin Yuc, Shuanglin Chena
a Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China;
b College of Pharmacy, the Ohio State University, Columbus, OH 43210, USA;
c Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Abstract:
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) 2D 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 caspase inhibitors 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, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.
Key words:    Hypocrellin A    Photodynamic therapy    Reactive oxygen species    Proteomic    LC-MS/MS    iTRAQ   
Received: 2018-08-17     Revised: 2018-11-15
DOI: 10.1016/j.apsb.2018.12.004
Funds: This study was 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) and the Priority Academic Program Development of Jiangsu Higher Educational Institutions (China).
Corresponding author: Shuqin Yu, Shuanglin Chen     Email:yushuqin@njnu.edu.cn;chenshuanglin@njnu.edu.cn
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Shanshan Qi
Lingyuan Guo
Shuzhen Yan
Robert J. Lee
Shuqin Yu
Shuanglin Chen

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