Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells.
Phenylethyl isothiocyanate (PEITC), a hydrolysis compound of gluconasturtiin, is metabolized to N-acetylcysteine (NAC)-PEITC in the body after the consumption of cruciferous vegetables. We observed an inhibitory effect of PEITC and its metabolite NAC-PEITC on cancer cell proliferation, adhesion, invasion, migration and metastasis in SK-Hep1 human hepatoma cells. PEITC and NAC-PEITC suppressed SK-Hep1 cell proliferation in a dose-dependent manner, and exposure to 10 microM PEITC or NAC-PEITC reduced cell proliferation by 25% and 30%, respectively. NAC-PEITC inhibited cancer cell adhesion, invasion and migration to a similar or to an even larger degree than PEITC. The expression of matrix metalloproteinase (MMP) 2, MMP-9 and membrane type 1 matrix metalloproteinase (MT1-MMP) is a known risk factor for metastatic disease. Gelatin zymography analysis revealed a significant downregulation of MMP-2/MMP-9 protein expression in SK-Hep1 cells treated with 0.1-5 microM PEITC or NAC-PEITC. PEITC and NAC-PEITC treatment caused dose-dependent decreases in MMP-2/MMP-9 and MT1-MMP mRNA levels, as determined by reverse transcription polymerase chain reaction. PEITC and NAC-PEITC also increased the mRNA levels of tissue inhibitors of matrix metalloproteinase (TIMPs) 1 and 2. Our data suggest that this inhibition is mediated by downregulation of MMP and upregulation of TIMPs.
Department of Food Science and Technology, School of Agricultural Biotechnology and Center for Agricultural Biomaterials, College of Agriculture and Life Sciences, Seoul National University, San 56-1, Shillim-dong, Gwanak-gu 151-921, Republic of Korea.
Eun-Sun
ES
Hwang
Hyong Joo
HJ
Lee
D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D019715:Tissue Inhibitor of Metalloproteinase-1; C058305:phenethyl isothiocyanate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D000111:Acetylcysteine