Intestinal Metabolite Compound K of Ginseng Saponin Potently Attenuates Metastatic Growth of Hepatocellular Carcinoma by Augmenting Apoptosis via a Bid-Mediated Mitochondrial Pathway
Intestinal Metabolite Compound K of Ginseng Saponin Potently Attenuates Metastatic Growth of Hepatocellular Carcinoma by Augmenting Apoptosis via a Bid-Mediated Mitochondrial Pathway
复制标题
人参皂苷的肠道代谢物化合物 K 通过 Bid 介导的线粒体途径增强细胞凋亡，有效减弱肝细胞癌的转移性生长
DOI：
10.1021/jf103814f
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发表时间：
2010-12-22
影响因子：
6.1
通讯作者：
Hu, Tianhui
中科院分区：
文献类型：
--
作者：
Song, Gang;Guo, Shiguang;Hu, Tianhui
最近研究表明，人参皂苷的肠道细菌代谢产物K（CK）具有抗肝细胞癌（HCC）活性，Bid是HCC治疗的潜在药物靶点。本文报道了肌酸激酶通过Bid介导的线粒体途径诱导肝癌细胞凋亡的新机制。OK呈浓度和时间依赖性抑制肝癌细胞生长，高剂量的OK可诱导肝癌细胞凋亡。此外，有效剂量的CK在体内有效地抑制皮下肿瘤生长和自发性HOC转移。在分子水平上，免疫组织化学染色显示，与未治疗的对照组相比，OK治疗组皮下肿瘤和肝转移组织中的BID表达显着下降，这也意味着BID可能在肝癌的生长和进展中发挥关键作用。进一步的研究表明，在细胞毒性细胞凋亡过程中，全长Bid从细胞核易位到线粒体与线粒体释放细胞色素c相关，表明全长Bid足以激活HCC细胞中响应CK处理的线粒体细胞死亡途径。总而言之，这些结果不仅揭示了CK诱导的肝癌细胞中BID介导的线粒体途径，而且表明OK可能成为一种潜在的以BID为靶点的细胞毒性药物，用于预防和治疗肝癌。
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. OK dramatically inhibited HCC cells growth in concentration- and time-dependent manners, and a high dose of OK could induce HCC cell apoptotic cell death. Furthermore, the effective dose of CK potently attenuated the subcutaneous tumor growth and spontaneous HOC metastasis in vivo. At the molecular level, immunohistochemical staining revealed that Bid expression in subcutaneous tumor and liver metastasis tissues decreased dramatically in OK-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 OK may become a potential cytotoxic drug targeting Bid in the prevention and treatment of HCC.