Document Detail


EGCG inhibits mammary cancer cell migration through inhibition of nitric oxide synthase and guanylate cyclase.
MedLine Citation:
PMID:  18692479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor cell migration is considered as a major event in the metastatic cascade. Here we examined the effect of (-)-epigallocatechin-3-gallate (EGCG) on migration capacity and molecular mechanism using 4T1 murine mammary cancer cells as a model. Using an in vitro migration assay, we found that treatment of 4T1 cells with EGCG resulted in concentration-dependent inhibition of migration of these cells. The migration capacity of cells was reduced in presence of N(G)-nitro-l-arginine methyl ester (l-NAME), an inhibitor of nitric oxide synthase. EGCG suppressed the elevated levels of endogenous NO/NOS in 4T1 cells and blocked the migration promoting capacity of l-arginine. Treatment with guanylate cyclase inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinolalin-1-one (ODQ) reduced the migration of 4T1 cells. EGCG reduced the elevated levels of cGMP in cancer cells and blocked the migration restoring activity of 8-Br cGMP (cGMP analogue). These results indicate for the first time that EGCG inhibits mammary cancer cell migration through the inhibition of NO/NOS and guanylate cyclase.
Authors:
Thejass Punathil; Trygve O Tollefsbol; Santosh K Katiyar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-08-08
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  375     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2008-09-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  162-7     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, Birmingham, AL, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / pharmacology*
Carcinoma / enzymology*,  pathology
Catechin / analogs & derivatives*,  pharmacology
Cell Line, Tumor
Cell Movement / drug effects*
Cyclic GMP / metabolism
Enzyme Inhibitors / pharmacology
Guanylate Cyclase / antagonists & inhibitors*
Mammary Neoplasms, Animal / enzymology*,  pathology
Mice
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Nitrogen Oxides / antagonists & inhibitors,  metabolism
Oxadiazoles / pharmacology
Quinoxalines / pharmacology
Grant Support
ID/Acronym/Agency:
P30 AR050948-010001/AR/NIAMS NIH HHS; R01 CA129415/CA/NCI NIH HHS; R01 CA129415-01A1/CA/NCI NIH HHS; R01 CA129415-04/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Anticarcinogenic Agents; 0/Enzyme Inhibitors; 0/Nitrogen Oxides; 0/Oxadiazoles; 0/Quinoxalines; 154-23-4/Catechin; 50903-99-6/NG-Nitroarginine Methyl Ester; 7665-99-8/Cyclic GMP; BQM438CTEL/epigallocatechin gallate; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase
Comments/Corrections

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