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Compound K, a metabolite of ginseng saponin, induces apoptosis of hepatocellular carcinoma cells through the mitochondria-mediated caspase-dependent pathway

    作者

    Dong, X;Han, HB;Shi, HZ;Wang, TR;Wang, BY;Zhao, J

    作者单位

    [Dong, Xia; Han, Hongbo; Shi, Haizhou; Wang, Tingrui; Wang, Baoyun] Binzhou Cent Hosp, Binzhou Med Coll, Dept Gastrointestinal Surg, Binzhou, Peoples R China.;-;[Zhao, Jing] Shandong Univ, Dept Gastrointestinal Surg, Provincal Hosp, 324 Jingwuweiqi Rd, Jinan 250021, Shandong, Peoples R China.

    摘要

    Compound K (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. The purpose of this project was to detect whether CK has an anticancer effect on hepatocellular carcinoma (HCC) cells, and to further explore the possible mechanisms. The Hep-G2 cells and xenograft in nude mice were used as models to study the anticancer effect of CK. Methylthiazolyldiphenyl-tetrazolium-bromide (MTT) assay showed that CK significantly inhibited the viabilities of Hep-G2 cells in dose-and time-dependent manners. In addition, flow cytometry analysis showed that CK induced apoptosis and cell cycle arrest in Hep-G2 cells, which possibly accounted for the antiproliferative effects of CK. Notably, the data in the present research indicated that CK upregulated the expression of p21(Cip1) and p27(Kip1), and downregulated the expression of cyclin D1 and cyclin-dependent kinase 4, causing a G0/G1 phase arrest, blocking cell cycle progression, and inducing apoptosis in the Hep-G2 cells, which was mediated by the mitochondrial pathway through a modulation of the ratio of Bcl-2 to Bax. In vivo studies showed that tumor volume, compared with control group, was reduced dramatically in CK-treated group. Therefore, the present study provides new insights that CK may be an potential agents in the prevention or treatment of HCC.

    关键词

    ATTENUATES METASTATIC GROWTH; LUNG-CANCER CELLS; CYCLE PROGRESSION; IN-VITRO; RESISTANCE; ARREST; MODEL
基本信息

  • 所属机构:

    归属医师:

    UT:000406058200165

    刊名:INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE

    年,卷(期):2017年10卷7期

    页码:11146-11156

    附件:

    收录:   SCIE