title: EGCG inhibits mammary cancer cell migration through inhibition of nitric oxide synthase and guanylate cyclase.
abstract: 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.affiliation: Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, Birmingham, AL, USA.
authors.forename: Thejass
authors.initials: T
authors.lastname: Punathil
authors.forename: Trygve O
authors.initials: TO
authors.lastname: Tollefsbol
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D015674:Mammary Neoplasms, Animal / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009589:Nitrogen Oxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D011810:Quinoxalines; D002392:Catechin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester