title: Atrial natriuretic peptide and long acting natriuretic peptide inhibit MEK 1/2 activation in human prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center, Tampa, FL 33612, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Ehrentraud J
authors.initials: EJ
authors.lastname: Eichelbaum
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: David L
authors.initials: DL
authors.lastname: Vesely
mesh_terms: 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
chemical_list: 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