Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 375, Issue 1, Pages 162-167Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.07.157
Keywords
nitric oxide; epigallocatechin-3-gallate; guanylate cyclase; cancer cell migration; mammary cancer cells; nitric oxide synthase
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Funding
- NIH [R01 CA129415]
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Tumor cell migration is considered as a major event in the metastatic cascade. Here we examined the effect of (-)-epigallocatechlin-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]oxadiaxol[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. (C) 2008 Elsevier Inc. All rights reserved.
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