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Vessel dilator and kaliuretic peptide inhibit Ras in human prostate cancer cells.

AbstractBACKGROUND:
Vessel dilator and kaliuretic peptide have anticancer effects in human prostate adenocarcinomas.
MATERIALS AND METHODS:
The effects of vessel dilator, kaliuretic peptide and cyclic GMP on Ras were examined in human prostate adenocarcinoma cells.
RESULTS:
Vessel dilator and kaliuretic peptide decreased the activation of Ras -GTP over a concentration range of 0.01 microM to 1 microM. Vessel dilator and kaliuretic peptide (each 1 muM) inhibited the phosphorylation of Ras by 95% (p<0.0001) and 90% (p<0.0001), respectively. At 0.01 microM of kaliuretic peptide, the maximal inhibition was 95% . The inhibition of Ras lasted for 48 to 72 hours secondary to both peptides. Their ability to inhibit Ras was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited Ras phosphorylation (89%; p=0.0015).
CONCLUSION:
Vessel dilator and kaliuretic peptide both inhibit Ras partially mediated via cyclic GMP as part of their anticancer mechanism(s) of action.
AuthorsYing Sun, Ehrentraud J Eichelbaum, William P Skelton 4th, Anne Lenz, Hai Wang, David L Vesely
JournalAnticancer research (Anticancer Res) Vol. 29 Issue 4 Pg. 971-5 (Apr 2009) ISSN: 0250-7005 [Print] Greece
PMID19414334 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Peptide Fragments
  • Protein Precursors
  • atrial natriuretic factor precursor (79-98)
  • atrial natriuretic factor prohormone (31-67)
  • Guanosine Diphosphate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Atrial Natriuretic Factor
  • ras Proteins
  • Sodium-Potassium-Exchanging ATPase
  • Cyclic GMP
Topics
  • Adenocarcinoma (drug therapy, metabolism, secondary)
  • Aged
  • Atrial Natriuretic Factor (pharmacology)
  • Cyclic GMP (pharmacology)
  • Guanosine 5'-O-(3-Thiotriphosphate) (metabolism)
  • Guanosine Diphosphate (metabolism)
  • Humans
  • Immunoblotting
  • Male
  • Natriuresis
  • Peptide Fragments (pharmacology)
  • Prostatic Neoplasms (drug therapy, metabolism, pathology)
  • Protein Precursors (pharmacology)
  • Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors)
  • Tumor Cells, Cultured
  • ras Proteins (antagonists & inhibitors, metabolism)

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