Atrial natriuretic peptide and long acting natriuretic peptide inhibit MEK 1/2 activation in human prostate cancer cells.
BACKGROUND
Atrial natriuretic peptide and long acting natriuretic peptide have anticancer effects in human prostate adenocarcinomas.


METHODS
Atrial natriuretic peptide, long acting natriuretic peptide and cyclic GMP's effects on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells.


RESULTS
Atrial natriuretic peptide and long acting natriuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 microM to 10 microM. Long acting natriuretic peptide and atrial natriuretic peptide (each 10 microM) inhibited the phosphorylation of MEK 1/2 kinase 97% (p < 0.00001) and 88% (p < 0.00001), respectively. The inhibition of MEK 1/2 was maximal at two hours, and ceased by four hours, secondary to both peptides. The ability of peptides to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation by 93%.


CONCLUSIONS
Atrial natriuretic peptide and long acting natriuretic peptide both inhibit MEK 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, FL 33612, USA.
Eichelbaum
Ehrentraud J
EJ
Wang
Hai
H
Vesely
David L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000906:Antibodies; D010446:Peptide Fragments; C054547:atrial natriuretic factor prohormone (1-30), human; D009320:Atrial Natriuretic Factor; C482128:MAP2K2 protein, human; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D006152:Cyclic GMP