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.


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).


CONCLUSIONS
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.
Sun
Ying
Y
Department of Internal Medicine, University of South Florida Cardiac Hormone Center, and James A. Haley Veterans Medical Center-151, Tampa, Florida 33612, U.S.A.
Eichelbaum
Ehrentraud J
EJ
Lenz
Anne
A
Skelton
William P
WP
Wang
Hai
H
Vesely
David L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015153:Blotting, Western; D006152:Cyclic GMP / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D010446:Peptide Fragments; C054547:atrial natriuretic factor prohormone (1-30), human; D009320:Atrial Natriuretic Factor; D018631:ras Proteins; D006152:Cyclic GMP