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Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3
- Source :
- Molecules, Volume 23, Issue 6, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules, Vol 23, Iss 6, p 1482 (2018)
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- The ginsenoside compound K (20-O-&beta<br />d-glucopyranosyl-20(S)-protopanaxadiol<br />CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells<br />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 and apoptosis by inhibiting p-STAT3 in human liver cancer cells<br />thus, CK might be a potential therapeutic candidate for human HCC.
- Subjects :
- 0301 basic medicine
Ginsenosides
Pharmaceutical Science
Analytical Chemistry
STAT3
Mice
chemistry.chemical_compound
0302 clinical medicine
Drug Discovery
Endoplasmic Reticulum Chaperone BiP
Mice, Inbred BALB C
biology
Chemistry
Liver Neoplasms
apoptosis
Hep G2 Cells
hepatoma
Endoplasmic Reticulum Stress
Neoplasm Proteins
CK
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Molecular Medicine
Protopanaxadiol
Female
ERS
Liver cancer
STAT3 Transcription Factor
Carcinoma, Hepatocellular
Mice, Nude
ginsenoside
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
medicine
Animals
Humans
Gene silencing
Physical and Theoretical Chemistry
Endoplasmic reticulum
Organic Chemistry
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Apoptosis
Cancer cell
Cancer research
Unfolded protein response
biology.protein
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....2a6d601ef146127be0b7815bece24c8f