title: CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression.
abstract: Clinical observations suggest that hepatocyte growth factor (HGF) can promote invasion and metastasis in hepatocellular carcinoma. In this study, we found that HGF-stimulated invasion of SK-Hep-1 cells, together with increased expression of matrix metalloproteinase (MMP)-9. CHM-1 was identified from 2-phenyl-4-quinolone derivatives to potently inhibit HGF-induced cell invasion, proteolytic activity, and expression of MMP-9. CHM-1 significantly inhibited tyrosine autophosphorylation of c-Met induced by HGF. CHM-1 also suppressed HGF-induced Akt phosphorylation, and NF-kappaB activation, the downstream regulators of HGF/c-Met signaling, resulting in the inhibition of MMP-9. Thus, we suggest that CHM-1 is a potential therapeutic agent against tumor invasion.
authors: Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan.
authors: Shih-Wei
authors: SW
authors: Wang
authors: Shiow-Lin
authors: SL
authors: Pan
authors: Chieh-Yu
authors: CY
authors: Peng
authors: Der-Yi
authors: DY
authors: Huang
authors: An-Chi
authors: AC
authors: Tsai
authors: Ya-Ling
authors: YL
authors: Chang
authors: Jih-Hwa
authors: JH
authors: Guh
authors: Sheng-Chu
authors: SC
authors: Kuo
authors: Kuo-Hsiung
authors: KH
authors: Lee
authors: Che-Ming
authors: CM
authors: Teng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004149:Dioxoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C525063:2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone; D000970:Antineoplastic Agents; D004149:Dioxoles; D016328:NF-kappa B; D015363:Quinolones; D017228:Hepatocyte Growth Factor; D051550:I-kappa B Kinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9