Vessel dilator and kaliuretic peptide inhibit Ras in human prostate cancer cells.

BACKGROUND Vessel dilator and kaliuretic peptide have anticancer effects in human prostate adenocarcinomas. MATERIALS AND METHODS The effects of vessel dilator, kaliuretic peptide and cyclic GMP on Ras were examined in human prostate adenocarcinoma cells. RESULTS Vessel dilator and kaliuretic peptide decreased the activation of Ras -GTP over a concentration range of 0.01 microM to 1 microM. Vessel dilator and kaliuretic peptide (each 1 muM) inhibited the phosphorylation of Ras by 95% (p<0.0001) and 90% (p<0.0001), respectively. At 0.01 microM of kaliuretic peptide, the maximal inhibition was 95% . The inhibition of Ras lasted for 48 to 72 hours secondary to both peptides. Their ability to inhibit Ras was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited Ras phosphorylation (89%; p=0.0015). CONCLUSION Vessel dilator and kaliuretic peptide both inhibit Ras partially mediated via cyclic GMP as part of their anticancer mechanism(s) of action.