Vessel dilator and kaliuretic peptide inhibit ERK 1/2 activation in human prostate cancer cells.

BACKGROUND Vessel dilator and kaliuretic peptide have anticancer effects in human prostate adenocarcinomas. MATERIALS AND METHODS Vessel dilator, kaliuretic peptide and cyclic GMP's effects on ERK 1/2 kinase were examined in human prostate adenocarcinoma cells. RESULTS Vessel dilator and kaliuretic peptide decreased the activation of ERK 1/2 over a concentration range of 0.01 microM to 1 microM. Vessel dilator and kaliuretic peptide (each 1 microM) inhibited the phosphorylation of ERK 1/2 kinase 96% (p < 0.0001) and 70% (p < 0.001), respectively. Both had significant effects within five minutes at their 0.01 microM concentrations. The inhibition of ERK 1/2 lasted for at least two hours secondary to both. Their ability to inhibit ERK 1/2 was decreased by cyclic GMP antibody and cyclic GMP itself decreased ERK 1/2 phosphorylation. CONCLUSION Vessel dilator and kaliuretic peptide both inhibit ERK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.