Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer.
Identifieur interne : 000C31 ( Main/Exploration ); précédent : 000C30; suivant : 000C32Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer.
Auteurs : Zheng-Hai Tang [République populaire de Chine] ; Wen-Xiang Cao [République populaire de Chine] ; Xia Guo [République populaire de Chine] ; Xiao-Yang Dai [République populaire de Chine] ; Jia-Hong Lu [République populaire de Chine] ; Xiuping Chen [République populaire de Chine] ; Hong Zhu [République populaire de Chine] ; Jin-Jian Lu [République populaire de Chine]Source :
- Cancer letters [ 1872-7980 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Antinéoplasiques (pharmacologie), Autophagie (), Benzylisoquinoléines (pharmacologie), Carcinome pulmonaire non à petites cellules (anatomopathologie), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Cathepsines (métabolisme), Concentration en ions d'hydrogène, Humains, Lignée cellulaire tumorale, Quinazolinones (pharmacologie), Récepteurs ErbB (antagonistes et inhibiteurs), Souris, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- anatomopathologie : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- antagonistes et inhibiteurs : Récepteurs ErbB.
- métabolisme : Cathepsines.
- pharmacologie : Antinéoplasiques, Benzylisoquinoléines, Quinazolinones.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- Animaux, Autophagie, Concentration en ions d'hydrogène, Humains, Lignée cellulaire tumorale, Souris.
English descriptors
- KwdEn :
- Animals, Antineoplastic Agents (pharmacology), Autophagy (drug effects), Benzylisoquinolines (pharmacology), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (pathology), Cathepsins (metabolism), Cell Line, Tumor, ErbB Receptors (antagonists & inhibitors), Humans, Hydrogen-Ion Concentration, Lung Neoplasms (drug therapy), Lung Neoplasms (pathology), Mice, Quinazolinones (pharmacology).
- MESH :
- chemical , antagonists & inhibitors : ErbB Receptors.
- chemical , metabolism : Cathepsins.
- chemical , pharmacology : Antineoplastic Agents, Benzylisoquinolines, Quinazolinones.
- drug effects : Autophagy.
- drug therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- Animals, Cell Line, Tumor, Humans, Hydrogen-Ion Concentration, Mice.
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.
DOI: 10.1016/j.canlet.2017.10.001
PubMed: 29024815
Affiliations:
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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.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Zhejiang</li></region><settlement><li>Hangzhou</li></settlement><orgName><li>Université de Zhejiang</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Tang, Zheng Hai" sort="Tang, Zheng Hai" uniqKey="Tang Z" first="Zheng-Hai" last="Tang">Zheng-Hai Tang</name></noRegion><name sortKey="Cao, Wen Xiang" sort="Cao, Wen Xiang" uniqKey="Cao W" first="Wen-Xiang" last="Cao">Wen-Xiang Cao</name><name sortKey="Chen, Xiuping" sort="Chen, Xiuping" uniqKey="Chen X" first="Xiuping" last="Chen">Xiuping Chen</name><name sortKey="Dai, Xiao Yang" sort="Dai, Xiao Yang" uniqKey="Dai X" first="Xiao-Yang" last="Dai">Xiao-Yang Dai</name><name sortKey="Guo, Xia" sort="Guo, Xia" uniqKey="Guo X" first="Xia" last="Guo">Xia Guo</name><name sortKey="Lu, Jia Hong" sort="Lu, Jia Hong" uniqKey="Lu J" first="Jia-Hong" last="Lu">Jia-Hong Lu</name><name sortKey="Lu, Jin Jian" sort="Lu, Jin Jian" uniqKey="Lu J" first="Jin-Jian" last="Lu">Jin-Jian Lu</name><name sortKey="Zhu, Hong" sort="Zhu, Hong" uniqKey="Zhu H" first="Hong" last="Zhu">Hong Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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