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Baicalin promoted site-2 protease and not site-1 protease in endoplasmic reticulum stress-induced apoptosis of human hepatocellular carcinoma cells.

Abstract：

:Baicalin (5,6-dihydroxy-7-o-glucuronide flavone) is an extract from the roots of Chinese herb Huang Qin (Scutellaria baicalensis Georgi) and is reported to have antioxidative, antiproliferative, anti-inflammatory, and anticancer activities. This study aimed to investigate the inhibitory effect of baicalin on human hepatocellular carcinoma (HCC) cells and the involvement of endoplasmic reticulum stress-induced cell apoptosis. Two human HCC cell lines, HepG2 and SMMC7221, were used in this study. The cells were incubated with baicalin solutions at various concentrations. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell proliferation inhibition; a TUNEL assay was used to evaluate cell apoptosis; small RNA interference was applied to silence IRE1, ATF6, and protein kinase R-like ER kinase (PERK), which are transmembrane proteins inducing cell apoptosis, and two proteases (S1P and S2P) which cleave ATF6. Real-time PCR was used to evaluate the silencing effects of specific siRNA. Expression levels of specific proteins were analyzed by western blotting. Baicalin was found to inhibit the proliferation of HCC cells by inducing apoptosis in a concentration-dependent manner. Elevated expression levels of GRP78, CHOP, p50-ATF6, and caspase12 were found after baicalin incubation. Compared with IRE1 and PERK silencing, ATF6 knockdown dramatically impaired baicalin's apoptosis-inducing activity. Furthermore, S2P silencing, rather than S1P silencing, was also found to impair baicalin-induced HCC cell apoptosis significantly. In conclusion, (a) baicalin inhibits human HCC cells by inducing apoptosis; (b) baicalin induces cell apoptosis by activating ATF6 signaling pathway in endoplasmic reticulum (ER) stress;

journal_name

FEBS Open Bio

journal_title

FEBS open bio

authors

Yu Z,Luo X,Wang C,Ye J,Liu S,Xie L,Wang F,Bao J

doi

10.1002/2211-5463.12130

subject

Has Abstract

pub_date

2016-10-24 00:00:00

pages

1093-1101

issue

issn

2211-5463

pii

FEB412130

journal_volume

pub_type

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Baicalin promoted site-2 protease and not site-1 protease in endoplasmic reticulum stress-induced apoptosis of human hepatocellular carcinoma cells.