Atrial natriuretic peptide and long acting natriuretic peptide inhibit MEK 1/2 activation in human prostate cancer cells.

BACKGROUND

Atrial natriuretic peptide and long acting natriuretic peptide have anticancer effects in human prostate adenocarcinomas.

MATERIALS AND METHODS

Atrial natriuretic peptide, long acting natriuretic peptide and cyclic GMP's effects on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells.

RESULTS

Atrial natriuretic peptide and long acting natriuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 microM to 10 microM. Long acting natriuretic peptide and atrial natriuretic peptide (each 10 microM) inhibited the phosphorylation of MEK 1/2 kinase 97% (p < 0.00001) and 88% (p < 0.00001), respectively. The inhibition of MEK 1/2 was maximal at two hours, and ceased by four hours, secondary to both peptides. The ability of peptides to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation by 93%.

CONCLUSION

Atrial natriuretic peptide and long acting natriuretic peptide both inhibit MEK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.