Vessel dilator and kaliuretic peptide inhibit ERK 1/2 activation in human prostate cancer cells.
BACKGROUND
Vessel dilator and kaliuretic peptide have anticancer effects in human prostate adenocarcinomas.


METHODS
Vessel dilator, kaliuretic peptide and cyclic GMP's effects on ERK 1/2 kinase were examined in human prostate adenocarcinoma cells.


RESULTS
Vessel dilator and kaliuretic peptide decreased the activation of ERK 1/2 over a concentration range of 0.01 microM to 1 microM. Vessel dilator and kaliuretic peptide (each 1 microM) inhibited the phosphorylation of ERK 1/2 kinase 96% (p < 0.0001) and 70% (p < 0.001), respectively. Both had significant effects within five minutes at their 0.01 microM concentrations. The inhibition of ERK 1/2 lasted for at least two hours secondary to both. Their ability to inhibit ERK 1/2 was decreased by cyclic GMP antibody and cyclic GMP itself decreased ERK 1/2 phosphorylation.


CONCLUSIONS
Vessel dilator and kaliuretic peptide 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
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009318:Natriuresis; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011498:Protein Precursors / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP