Journal
MOLECULAR CARCINOGENESIS
Volume 48, Issue 3, Pages 232-242Publisher
WILEY
DOI: 10.1002/mc.20473
Keywords
nitric oxide; mitogen-activated protein kinase; grape seed proanthocyanidins; guanylate cyclase; tumor cell migration; lung cancer cells
Categories
Ask authors/readers for more resources
Tumor cell migration is considered as a major event in the metastatic cascade. Here we examined the effect of grape seed proanthocyanidins (GSPs) on migration capacity and signaling mechanisms using nonsmall cell human lung cancer cells. Using in vitro migration assay, we found that treatment of A549 and H 1299 cells with GSPs 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. GSPs suppressed the elevated levels of endogenous NO/NOS in A549 and H1299 cells and blocked the migration promoting capacity of L-arginine. Treatment with guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinoialin-1-one (ODQ) reduced the migration of A549 cells whereas additional presence of 8-bromoguanosine 3'5'-cyclic monophosphate (8-Br-cGMP, cGMP analogue) restored the migration of these cells, suggesting a role for GC in migration of A549 cells. GSPs reduced the elevated levels of cGMP in cancer cells and also blocked the migration restoring activity of 8-Br-cGMP. The mitogen-activated protein kinase kinase (MAPKK) inhibitor, UO126, inhibited the migration of A549 cells, indicating a role for MAPKK in the migration. Additionally, UO126 and ODQ inhibited the migration restoring effects Of L-arginine in L-NAME-treated cells, suggesting the involvement of cGMP and MAPK pathways in NO-mediated migration. GSPs inhibited L-arginine and 8-Br-cGMP-induced activation of ERK1/2 in A549 cells. Together, these results indicate sequential inhibition of NOMOS, GC, and MAPK pathways by GSPs in mediating the inhibitory signals for cell migration, an essential step in invasion and metastasis. (C) 2008 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available