Molecules, Vol. 23, Pages 1482: Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3
Molecules, Vol. 23, Pages 1482: Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3
Molecules doi: 10.3390/molecules23061482
Authors:
Xuan Zhang
Silin Zhang
Qitong Sun
Wenjun Jiao
Yan Yan
Xuewu Zhang
The ginsenoside compound K (20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we demonstrated that CK inhibited the growth and colony formation of HepG2 and SMMC-7721 cells, phenotypes that were mediated by inducing apoptosis. Meanwhile, CK showed lower toxicity in normal hepatoma cells. After treating HepG2 and SMMC-7721 cells with CK, p-STAT3 levels decreased, the three branches of the unfolded protein response were activated, and levels of endoplasmic reticulum stress (ERS)-related proteins were increased. We also revealed that CK decreased the DNA-binding capacity of STAT3. Moreover, silencing STAT3 with CRISPR/Cas9 technology enhanced CK-induced ERS and apoptosis. Finally, we showed that CK inhibited the growth of liver cancer xenografts with little toxicity. Mice bearing human HCC xenografts that were treated with CK showed increased GRP78 expression and decreased p-STAT3 levels. Taken together, these data showed that CK induced ERS a...
Source: Molecules - Category: Chemistry Authors: Xuan Zhang Silin Zhang Qitong Sun Wenjun Jiao Yan Yan Xuewu Zhang Tags: Article Source Type: research
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