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.


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).


CONCLUSIONS
Vessel dilator and kaliuretic peptide both inhibit Ras partially mediated via cyclic GMP as part of their anticancer mechanism(s) of action.
USF Cardiac Hormone Center, J.A. Haley Veterans Medical Center, Tampa, Florida 33612, USA.
Ying
Y
Sun
Ehrentraud J
EJ
Eichelbaum
William P
WP
Skelton
Anne
A
Lenz
Hai
H
Wang
David L
DL
Vesely
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009318:Natriuresis; D010446:Peptide Fragments / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009320:Atrial Natriuretic Factor; D018631:ras Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP