Cargando…
Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR
Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases worldwide with limited options for effective treatment. Biomarker-based active compound targeting therapy may shed some light on novel drugs for HCC. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696242/ https://www.ncbi.nlm.nih.gov/pubmed/29190976 http://dx.doi.org/10.18632/oncotarget.21750 |
_version_ | 1783280409050611712 |
---|---|
author | Ren, Bo Liu, Hui Gao, Hang Liu, Shutong Zhang, Zehui Fribley, Andrew M. Callaghan, Michael U. Xu, Zhixiang Zeng, Qinghua Li, Yulin |
author_facet | Ren, Bo Liu, Hui Gao, Hang Liu, Shutong Zhang, Zehui Fribley, Andrew M. Callaghan, Michael U. Xu, Zhixiang Zeng, Qinghua Li, Yulin |
author_sort | Ren, Bo |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases worldwide with limited options for effective treatment. Biomarker-based active compound targeting therapy may shed some light on novel drugs for HCC. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play important roles in the regulation of cell fate and have become novel signaling targets for the development of anticancer drugs. Celastrol, a triterpene from traditional Chinese medicine, has been reported to possess anti-tumor effects on various cancers. We, along with several other research groups, have recently reported that UPR was induced by celastrol in several different cancers, including hepatocellular carcinoma. However, UPR status in HCC still remains unclear. The role of ER stress and autophagy in response to celastrol also has yet to be elucidated. Our results demonstrated that celastrol could cause G2/M phase rest and inhibit proliferation in HepG2 and Bel7402. Exposure to celastrol resulted in the activation of the intrinsic apoptotic pathway, via ER stress and the UPR. In murine syngeneic model studies celastrol inhibited H22 tumor growth via the induction of ER stress and apoptosis. Our study suggests that celastrol is a potential drug for HCC therapy via targeting ER-stress/UPR. |
format | Online Article Text |
id | pubmed-5696242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56962422017-11-29 Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR Ren, Bo Liu, Hui Gao, Hang Liu, Shutong Zhang, Zehui Fribley, Andrew M. Callaghan, Michael U. Xu, Zhixiang Zeng, Qinghua Li, Yulin Oncotarget Research Paper Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases worldwide with limited options for effective treatment. Biomarker-based active compound targeting therapy may shed some light on novel drugs for HCC. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play important roles in the regulation of cell fate and have become novel signaling targets for the development of anticancer drugs. Celastrol, a triterpene from traditional Chinese medicine, has been reported to possess anti-tumor effects on various cancers. We, along with several other research groups, have recently reported that UPR was induced by celastrol in several different cancers, including hepatocellular carcinoma. However, UPR status in HCC still remains unclear. The role of ER stress and autophagy in response to celastrol also has yet to be elucidated. Our results demonstrated that celastrol could cause G2/M phase rest and inhibit proliferation in HepG2 and Bel7402. Exposure to celastrol resulted in the activation of the intrinsic apoptotic pathway, via ER stress and the UPR. In murine syngeneic model studies celastrol inhibited H22 tumor growth via the induction of ER stress and apoptosis. Our study suggests that celastrol is a potential drug for HCC therapy via targeting ER-stress/UPR. Impact Journals LLC 2017-10-10 /pmc/articles/PMC5696242/ /pubmed/29190976 http://dx.doi.org/10.18632/oncotarget.21750 Text en Copyright: © 2017 Ren et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Ren, Bo Liu, Hui Gao, Hang Liu, Shutong Zhang, Zehui Fribley, Andrew M. Callaghan, Michael U. Xu, Zhixiang Zeng, Qinghua Li, Yulin Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title | Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title_full | Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title_fullStr | Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title_full_unstemmed | Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title_short | Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR |
title_sort | celastrol induces apoptosis in hepatocellular carcinoma cells via targeting er-stress/upr |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696242/ https://www.ncbi.nlm.nih.gov/pubmed/29190976 http://dx.doi.org/10.18632/oncotarget.21750 |
work_keys_str_mv | AT renbo celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT liuhui celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT gaohang celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT liushutong celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT zhangzehui celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT fribleyandrewm celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT callaghanmichaelu celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT xuzhixiang celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT zengqinghua celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr AT liyulin celastrolinducesapoptosisinhepatocellularcarcinomacellsviatargetingerstressupr |