Cargando…
Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation
Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC)...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271537/ https://www.ncbi.nlm.nih.gov/pubmed/24662070 http://dx.doi.org/10.3390/molecules19033508 |
_version_ | 1783376950568419328 |
---|---|
author | Fan, Xing-Xing Li, Na Wu, Jian-Lin Zhou, Yan-Ling He, Jian-Xing Liu, Liang Leung, Elaine Lai-Han |
author_facet | Fan, Xing-Xing Li, Na Wu, Jian-Lin Zhou, Yan-Ling He, Jian-Xing Liu, Liang Leung, Elaine Lai-Han |
author_sort | Fan, Xing-Xing |
collection | PubMed |
description | Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is not clearly known. Here, we examined the potency of celastrol in three different NSCLC cell lines. We explored its treatment mechanism in two gefitinib-resistant NSCLC cell lines (H1650 and H1975). Our data demonstrated that celastrol exerted its apoptotic effect in a dose- and time-dependent manner. Also, the mitochondria membrane potential was gradually lost and the ratio of Bax/Bcl-2 increased after the treatment of celastrol, both of which are indicators of mitochondria membrane integrity. Although the caspases were activated, the treatment with pan-caspase inhibitor could partially inhibit the level of apoptosis. Moreover, the protein level of Hsp90 client proteins, EGFR and AKT, was measured. Interestingly, both client proteins were remarkably down-regulated after the treatment of celastrol. Taken together, our data showed that celastrol may be developed as a promising agent for treating gefitinib-resistant NSCLCs by inducing apoptosis through caspase-dependent pathways and Hsp90 client protein degradation. |
format | Online Article Text |
id | pubmed-6271537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62715372018-12-20 Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation Fan, Xing-Xing Li, Na Wu, Jian-Lin Zhou, Yan-Ling He, Jian-Xing Liu, Liang Leung, Elaine Lai-Han Molecules Article Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is not clearly known. Here, we examined the potency of celastrol in three different NSCLC cell lines. We explored its treatment mechanism in two gefitinib-resistant NSCLC cell lines (H1650 and H1975). Our data demonstrated that celastrol exerted its apoptotic effect in a dose- and time-dependent manner. Also, the mitochondria membrane potential was gradually lost and the ratio of Bax/Bcl-2 increased after the treatment of celastrol, both of which are indicators of mitochondria membrane integrity. Although the caspases were activated, the treatment with pan-caspase inhibitor could partially inhibit the level of apoptosis. Moreover, the protein level of Hsp90 client proteins, EGFR and AKT, was measured. Interestingly, both client proteins were remarkably down-regulated after the treatment of celastrol. Taken together, our data showed that celastrol may be developed as a promising agent for treating gefitinib-resistant NSCLCs by inducing apoptosis through caspase-dependent pathways and Hsp90 client protein degradation. MDPI 2014-03-21 /pmc/articles/PMC6271537/ /pubmed/24662070 http://dx.doi.org/10.3390/molecules19033508 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Fan, Xing-Xing Li, Na Wu, Jian-Lin Zhou, Yan-Ling He, Jian-Xing Liu, Liang Leung, Elaine Lai-Han Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title | Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title_full | Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title_fullStr | Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title_full_unstemmed | Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title_short | Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation |
title_sort | celastrol induces apoptosis in gefitinib-resistant non-small cell lung cancer cells via caspases-dependent pathways and hsp90 client protein degradation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271537/ https://www.ncbi.nlm.nih.gov/pubmed/24662070 http://dx.doi.org/10.3390/molecules19033508 |
work_keys_str_mv | AT fanxingxing celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT lina celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT wujianlin celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT zhouyanling celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT hejianxing celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT liuliang celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation AT leungelainelaihan celastrolinducesapoptosisingefitinibresistantnonsmallcelllungcancercellsviacaspasesdependentpathwaysandhsp90clientproteindegradation |