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Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer
Tang, Zheng-Hai1; Cao, Wen-Xiang1; Guo, Xia1; Dai, Xiao-Yang2; Lu, Jia-Hong1; Chen, Xiuping1; Zhu, Hong2; Lu, Jin-Jian1
2018-01
Source PublicationCANCER LETTERS
ISSN0304-3835
Volume412Pages:1-9
Abstract

Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells. The potential mechanism of the CEP-inhibited autophagy was by blockage of autophagosome-lysosome fusion and inhibition of lysosomal cathepsin B and cathepsin D maturation. Furthermore, we found for the first time that dacomitinib (DAC), a second-generation epidermal growth factor receptor inhibitor that in the phase III clinical trials for NSCLC treatment, induced a protective autophagy to decrease its anti-cancer effect. Combined treatment with CEP increased the anti proliferative and apoptotic effects of DAC in vitro and enhanced the anti-cancer effect of DAC in NCI H1975 xenograft mice. Collectively, CEP might be further developed as an autophagic inhibitor, and combined treatment of CEP and DAC could offer an effective strategy for NSCLC treatment. (C) 2017 Elsevier B.V. All rights reserved.

KeywordCepharanthine Autophagy Lysosome Dacomitinib Nsclc
DOI10.1016/j.canlet.2017.10.001
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000418109100001
PublisherELSEVIER IRELAND LTD
The Source to ArticleWOS
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Zhejiang Province Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Tang, Zheng-Hai,Cao, Wen-Xiang,Guo, Xia,et al. Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer[J]. CANCER LETTERS,2018,412:1-9.
APA Tang, Zheng-Hai.,Cao, Wen-Xiang.,Guo, Xia.,Dai, Xiao-Yang.,Lu, Jia-Hong.,...&Lu, Jin-Jian.(2018).Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer.CANCER LETTERS,412,1-9.
MLA Tang, Zheng-Hai,et al."Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer".CANCER LETTERS 412(2018):1-9.
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