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Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells
Tang, Zheng-Hai; Cao, Wen-Xiang; Su, Min-Xia; Chen, Xiuping; Lu, Jin-Jian
2017-04-15
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN0041-008X
Volume321Pages:18-26
Abstract

Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. The OSI-induced expression of LC3-II was further increased when combined treatment with chloroquine (CQ), an autophagy inhibitor, and the mRFP-EGFP-LC3 plasmid-transfected cells exposed to OSI led to the production of more red-fluorescent puncta than green-fluorescent puncta, indicating OSI induced autophagic flux in the NSCLC cells. Knockdown of EGFR showed no effect on the OSI-induced expression of LC3-II in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC), catalase (CAT), or vitamin E (Vita E) significantly inhibited OSI-induced the accumulations of cytoplasmic vacuoles, the expression of LC3-II, as well as the formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change the OSI-induced cell viability decrease, whereas the OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC, CAT, and Vita E, respectively. Taken together, this is the first report that OSI induces an accompanied autophagy and the generation of ROS is critical for the OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. (C) 2017 Elsevier Inc. All rights reserved.

KeywordOsimertinib Azd9291 Autophagy Apoptosis Ros
DOI10.1016/j.taap.2017.02.017
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000397351900002
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
The Source to ArticleWOS
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被引频次[WOS]:19   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
AffiliationState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
First Author AffilicationInstitute of Chinese Medical Sciences
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Tang, Zheng-Hai,Cao, Wen-Xiang,Su, Min-Xia,et al. Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2017,321:18-26.
APA Tang, Zheng-Hai,Cao, Wen-Xiang,Su, Min-Xia,Chen, Xiuping,&Lu, Jin-Jian.(2017).Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells.TOXICOLOGY AND APPLIED PHARMACOLOGY,321,18-26.
MLA Tang, Zheng-Hai,et al."Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells".TOXICOLOGY AND APPLIED PHARMACOLOGY 321(2017):18-26.
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