Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells.
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Issue Date
2006-12
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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.Citation
J. Nutr. Biochem. 2006, 17 (12):837-846PubMed ID
16563723Additional Links
http://www.jnutbio.com/article/S0955-2863(06)00048-9/abstracthttp://patient-research.elsevier.com/patientresearch/displayAbs?key=S0955286306000489&referrer=http%253A%252F%252Fwww.ncbi.nlm.nih.gov%252Fsites%252Fentrez
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T8P-4JJGB3G-7&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=800ab93dc78506319f4b77d4fbbffd59
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ArticleLanguage
enDescription
Dietary modulation of carcinogenesis-related pathwaysDietary item or component studied:Phenylethyl isothiocyanate (PEITC), N-acetylcysteine (NAC)-PEITC Pathways studied:inhibition of MMP-2 and MMP-9 enzyme activities, influence metastasis (cell viability, adhesion, invasion) and migration.Study type (in vitro, animals, humans): SK-Hep1 human hepatocellular carcinoma cellsTissue/biological material/sample size:(5103/well) in 96-well plates, 24-well plates, six-well plateImpact on pathway (including dose-response):PEITC inhibited cell proliferation by 9.6-69%, cell numbers decreased by42% and 65% at 5 and 10 AM NAC-PEITC, cellular motility was controlled in a time-dependent manner, decreased MMP-9 expression by 21% and 30% with 1 and 5 AM PEITC, NACPEITC, treatment at 0.1-5 AM did not show any inhibitory effect on MMP-9 activity, The inhibition of MMP-2 mRNA expression was greater than that of MMP-9 mRNA, with 40% and 80% inhibition by 5 AM AITC and NAC-AITC, respectively. KEYWORDS CLASSIFICATION: analysis;Acetylcysteine;Agriculture;Antineoplastic Agents;Biotechnology;chemistry;Carcinoma,Hepatocellular;Cell Adhesion;Cell Movement;drug effects;drug therapy;dietary modulation of carcinogenesis-related pathways;Drug Screening Assays,Antitumor;Food;genetics;Humans;Isothiocyanates;Korea;Liver Neoplasms;metabolism;Matrix Metalloproteinase 14;Matrix Metalloproteinase 2;Matrix Metalloproteinase 9;Neoplasm Invasiveness;Neoplasm Metastasis;pathology;pharmacology;Research;Tissue Inhibitor of Metalloproteinase-1;Tumor Cells,Cultured.ISSN
0955-2863ae974a485f413a2113503eed53cd6c53
10.1016/j.jnutbio.2006.02.004
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