Atrial natriuretic peptide and long-acting natriuretic peptide inhibit ras in human prostate cancer cells.

BACKGROUND: Atrial natriuretic peptide and long-acting natriuretic peptide have anticancer effects in human prostate adenocarcinoma. MATERIALS AND METHODS: The effects of atrial natriuretic peptide and long-acting natriuretic peptide and cyclic GMP on Ras were examined in human prostate adenocarcinoma cells. RESULTS: Atrial natriuretic peptide and long-acting natriuretic peptide reduced the activation of Ras-GTP over a concentration range of 0.01 microM to 1 microM. Atrial natriuretic peptide and long-acting natriuretic peptide (each 0.1 microM) inhibited the phosphorylation of Ras 90% (p<0.0001) and 83% (p<0.0001), respectively. At 0.01 microM of long-acting natriuretic peptide, the maximal inhibition was 89%, which occurred within 5 minutes. Both peptide hormones inhibited Ras for 24 hours. Their ability to inhibit Ras was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited Ras phosphorylation (72%; p=0.009). CONCLUSION: Atrial natriuretic peptide and long-acting natriuretic peptide both inhibit Ras partially mediated via cyclic GMP as part of their anticancer mechanism(s) of action.