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


METHODS
The effect of vessel dilator, kaliuretic peptide and cyclic GMP on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells.


RESULTS
Vessel dilator and kaliuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 microM to 10 microM. Vessel dilator and kaliuretic peptide (each 10 microM) inhibited the phosphorylation of MEK 1/2 kinase by 98% (p < 0.0001) and 81% (p < 0.001), respectively. The inhibition of MEK 1/2 lasted for at least two hours, where it was maximal, secondary to both peptides. Their ability to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation.


CONCLUSIONS
Vessel dilator and kaliuretic 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, Florida 33612, USA.
Eichelbaum
Ehrentraud J
EJ
Wang
Hai
H
Vesely
David L
DL
D000230:Adenocarcinoma / Q000201:enzymology*; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011498:Protein Precursors / Q000494:pharmacology*
D000906:Antibodies; D000970:Antineoplastic Agents; D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D006152:Cyclic GMP