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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: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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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 |
Sumario: | 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. |
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