title: Anti-metastatic effects of ginsenoside Rd via inactivation of MAPK signaling and induction of focal adhesion formation.
abstract: Ginsenoside Rd is a protopanaxadiol-type ginsenoside found in ginseng and is the active ingredient in several Oriental herbal medicines. We investigated the effects of ginsenoside Rd on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2 and its possible mechanism of action. HepG2 cells were treated with ginsenoside Rd at different concentrations. Scratch wound and Boyden chamber assays were used to determine the effects of ginsenoside Rd on the migration and invasiveness of HepG2 cells, respectively. The molecular mechanisms by which ginsenoside Rd inhibited the invasion and migration of HepG2 cells were investigated by RT-PCR, Western blotting, gelatin zymography, promoter assay, and treatment with inhibitors of MAPK signaling. Immunofluorescence analysis was conducted to evaluate the effect of ginsenoside Rd on focal adhesion formation in HepG2 cells. Treatment with ginsenoside Rd dose- and time-dependently inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of MMP-1, MMP-2, and MMP-7, by blocking MAPK signaling by inhibiting the phosphorylation of ERK and p38 MAPK, by inhibition of AP-1 activation, and by inducing focal adhesion formation and modulating vinculin localization and expression. Treatment of HepG2 cells with ginsenoside Rd significantly inhibited metastasis, most likely by blocking MMP activation and MAPK signaling pathways involved in cancer cell migration. These findings may be useful for the development of novel chemotherapeutic agents for the treatment of malignant cancers.
authors: Department of Biotechnology, Bioenergy Research Center, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju 500-757, South Korea.
authors: Ji-Hae
authors: JH
authors: Yoon
authors: Yeo-Jin
authors: YJ
authors: Choi
authors: Seon-Woo
authors: SW
authors: Cha
authors: Seong-Gene
authors: SG
authors: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016596:Vinculin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D047428:Protein Kinase Inhibitors; C488955:VCL protein, human; D016596:Vinculin; D048051:p38 Mitogen-Activated Protein Kinases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1; C049863:ginsenoside Rd