EGCG inhibits mammary cancer cell migration through inhibition of nitric oxide synthase and guanylate cyclase.

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.