Atrial natriuretic peptide and long acting natriuretic peptide inhibit ERK 1/2 in prostate cancer cells.
BACKGROUND
Atrial natriuretic peptide (ANP) and long acting natriuretic peptide (LANP) have anticancer effects in human prostate adenocarcinomas.


METHODS
ANP, LANP and cyclic GMP's effects on extracellular signal-regulated kinase (ERK) 1/2 kinase were examined in human prostate adenocarcinoma cells.


RESULTS
ANP and LANP decreased the activation of ERK 1/2 over a concentration range of 0.01 microM to 10 microM. ANP and LANP's maximal inhibition of the phosphorylation of ERK 1/2 kinase were 94% and 88% (p < 0.0001), respectively. ANP had significant effects within five min at its 10 microM concentration. The inhibition of ERK 1/2 lasted for at least two h, where it was maximal, secondary to both peptides. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation.


CONCLUSIONS
ANP and LANP both inhibit ERK 1/2 kinase 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 Tampa, Florida 33612, USA.
Eichelbaum
Ehrentraud J
EJ
Wang
Hai
H
Vesely
David L
DL
D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology
D004791:Enzyme Inhibitors; D009320:Atrial Natriuretic Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D006152:Cyclic GMP