ReferenceID 336
Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer
Cancer Lett
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 inhibitor
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Record Fields
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- Reference Id
- 336
- Evidence Id
- 16926
- Core Evidence Id
- 16926
- Source Reference Id
- 642
- Herb2 Reference Id
- HBREF001081
- Subject Paper Key
- HBIN020124_29024815
- Pubmed Id
- 29024815
- Doi
- 10.1016/j.canlet.2017.10.001
- Paper Title
- Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer
- Paper 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.
- Journal
- Cancer Lett
- Publish Year
- 2018
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer
- Bilingual Status
- semi_complete