Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony...

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Main Authors:	Wang, Zhongxia, Jiang, Chunping, Chen, Weibo, Zhang, Guang, Luo, Dongjun, Cao, Yin, Wu, Junhua, Ding, Yitao, Liu, Baorui
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065687/

id	pubmed-4065687
recordtype	oai_dc
spelling	pubmed-40656872014-07-03 Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells Wang, Zhongxia Jiang, Chunping Chen, Weibo Zhang, Guang Luo, Dongjun Cao, Yin Wu, Junhua Ding, Yitao Liu, Baorui Research Article Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR) markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs) were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER) stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC. Hindawi Publishing Corporation 2014 2014-06-03 /pmc/articles/PMC4065687/ /pubmed/24995326 http://dx.doi.org/10.1155/2014/732516 Text en Copyright © 2014 Zhongxia Wang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Zhongxia Jiang, Chunping Chen, Weibo Zhang, Guang Luo, Dongjun Cao, Yin Wu, Junhua Ding, Yitao Liu, Baorui
spellingShingle	Wang, Zhongxia Jiang, Chunping Chen, Weibo Zhang, Guang Luo, Dongjun Cao, Yin Wu, Junhua Ding, Yitao Liu, Baorui Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
author_facet	Wang, Zhongxia Jiang, Chunping Chen, Weibo Zhang, Guang Luo, Dongjun Cao, Yin Wu, Junhua Ding, Yitao Liu, Baorui
author_sort	Wang, Zhongxia
title	Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
title_short	Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
title_full	Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
title_fullStr	Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
title_full_unstemmed	Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
title_sort	baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma cells
description	Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR) markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs) were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER) stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC.
publisher	Hindawi Publishing Corporation
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065687/
_version_	1612104512477069312

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

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