Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells.

5.00
Hdl Handle:
http://hdl.handle.net/10146/54093
Title:
Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells.
Authors:
Hwang, Eun-Sun; Lee, Hyong Joo
Abstract:
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):837-846
Journal:
The Journal of nutritional biochemistry
Issue Date:
Dec-2006
URI:
http://hdl.handle.net/10146/54093
DOI:
10.1016/j.jnutbio.2006.02.004
PubMed ID:
16563723
Additional Links:
http://www.jnutbio.com/article/S0955-2863(06)00048-9/abstract; http://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
Type:
Article
Language:
en
Description:
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:
0955-2863
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorHwang, Eun-Sun-
dc.contributor.authorLee, Hyong Joo-
dc.date.accessioned2009-03-11T09:49:58Z-
dc.date.available2009-03-11T09:49:58Z-
dc.date.issued2006-12-
dc.identifier.citationJ. Nutr. Biochem. 2006, 17 (12):837-846en
dc.identifier.issn0955-2863-
dc.identifier.pmid16563723-
dc.identifier.doi10.1016/j.jnutbio.2006.02.004-
dc.identifier.urihttp://hdl.handle.net/10146/54093-
dc.descriptionDietary 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.en
dc.description.abstractPhenylethyl 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.en
dc.language.isoenen
dc.relation.urlhttp://www.jnutbio.com/article/S0955-2863(06)00048-9/abstracten
dc.relation.urlhttp://patient-research.elsevier.com/patientresearch/displayAbs?key=S0955286306000489&referrer=http%253A%252F%252Fwww.ncbi.nlm.nih.gov%252Fsites%252Fentrezen
dc.relation.urlhttp://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=800ab93dc78506319f4b77d4fbbffd59en
dc.subjectPhenylethyl isothiocyanateen
dc.subjectN-acetylcysteineen
dc.subjectAdhesionen
dc.subjectInvasionen
dc.subjectMigrationen
dc.subjectMetastasisen
dc.subjectMatrix metalloproteinaseen
dc.subject.meshAcetylcysteine-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCarcinoma, Hepatocellular-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Movement-
dc.subject.meshDrug Screening Assays, Antitumor-
dc.subject.meshHumans-
dc.subject.meshIsothiocyanates-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMatrix Metalloproteinase 14-
dc.subject.meshMatrix Metalloproteinase 2-
dc.subject.meshMatrix Metalloproteinase 9-
dc.subject.meshNeoplasm Invasiveness-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshTissue Inhibitor of Metalloproteinase-1-
dc.subject.meshTumor Cells, Cultured-
dc.titlePhenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells.en
dc.typeArticleen
dc.identifier.journalThe Journal of nutritional biochemistryen
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