Intestinal metabolite compound K of ginseng saponin potently attenuates metastatic growth of hepatocellular carcinoma by augmenting apoptosis via a Bid-mediated mitochondrial pathway.
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.
Cancer Research Center, Medical College of Xiamen University, Xiamen 361005, China. gangsongsd@xmu.edu.cn
Gang
G
Song
Shiguang
S
Guo
Weiwei
W
Wang
Chun
C
Hu
Yubing
Y
Mao
Bing
B
Zhang
Hong
H
Zhang
Tianhui
T
Hu
D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009362:Neoplasm Metastasis; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D010936:Plant Extracts; D012503:Saponins