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Intestinal metabolite compound K of ginseng saponin potently attenuates metastatic growth of hepatocellular carcinoma by augmenting apoptosis via a Bid-mediated mitochondrial pathway.
- Source :
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Journal of agricultural and food chemistry [J Agric Food Chem] 2010 Dec 22; Vol. 58 (24), pp. 12753-60. Date of Electronic Publication: 2010 Dec 01. - Publication Year :
- 2010
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Abstract
- It was recently shown that compound K (CK), an intestinal bacterial metabolite of ginseng saponin, exhibits antihepatocellular carcinoma (HCC) activity, and Bid is a potential drug target for HCC therapy. This paper reports a novel mechanism of CK-induced apoptosis of HCC cells via Bid-mediated mitochondrial pathway. CK dramatically inhibited HCC cells growth in concentration- and time-dependent manners, and a high dose of CK could induce HCC cell apoptotic cell death. Furthermore, the effective dose of CK potently attenuated the subcutaneous tumor growth and spontaneous HCC metastasis in vivo. At the molecular level, immunohistochemical staining revealed that Bid expression in subcutaneous tumor and liver metastasis tissues decreased dramatically in CK-treated groups compared to untreated controls, which also implies that Bid may play a critical role in the growth and progression of HCC. Further study shows that translocation of full-length Bid to the mitochondria from nuclei during cytotoxic apoptosis was associated with the release of cytochrome c from mitochondria, indicating that full-length Bid is sufficient for the activation of mitochondrial cell death pathways in response to CK treatment in HCC cells. Taken together, the results not only reveal a Bid-mediated mitochondrial pathway in HCC cells induced by CK but also suggest that CK may become a potential cytotoxic drug targeting Bid in the prevention and treatment of HCC.
- Subjects :
- BH3 Interacting Domain Death Agonist Protein genetics
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular physiopathology
Cell Line, Tumor
Cell Proliferation drug effects
Humans
Intestinal Mucosa metabolism
Intestines drug effects
Liver Neoplasms drug therapy
Liver Neoplasms metabolism
Liver Neoplasms physiopathology
Mitochondria drug effects
Neoplasm Metastasis
Signal Transduction drug effects
Apoptosis drug effects
BH3 Interacting Domain Death Agonist Protein metabolism
Carcinoma, Hepatocellular pathology
Liver Neoplasms pathology
Mitochondria metabolism
Panax chemistry
Plant Extracts pharmacology
Saponins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 58
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21121651
- Full Text :
- https://doi.org/10.1021/jf103814f