CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression.
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.
Wang
Shih-Wei
SW
Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan.
Pan
Shiow-Lin
SL
Peng
Chieh-Yu
CY
Huang
Der-Yi
DY
Tsai
An-Chi
AC
Chang
Ya-Ling
YL
Guh
Jih-Hwa
JH
Kuo
Sheng-Chu
SC
Lee
Kuo-Hsiung
KH
Teng
Che-Ming
CM
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*
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