title: Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers.
abstract: BACKGROUND
  Mortality from renal-cell cancer remains a significant problem with an estimated 12,600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide have significant anti-cancer effects in breast, pancreatic, prostate and colon adenocarcinomas.
  
  
  METHODS
  These four peptide hormones plus brain natriuretic peptide (BNP), C-natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post-translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti-cancer effects in renal carcinomas.
  
  
  RESULTS
  Dose-response curves revealed a significant (P < 0.0001) decrease in human renal carcinoma cells with each 10-fold increase in concentration from 1 microm to 100 microm of five of these peptide hormones. There was an 81%, 74%, 66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and long-acting natriuretic peptide, respectively (P < 0.0001 for each), whereas BNP had no effect and CNP decreased renal cancer cell number by 10% (P = 0.04) at their 100 microm concentrations. Three days after treatment with these peptide hormones, the cancer cells began to proliferate again. The four cardiac hormones and urodilatin decreased DNA synthesis from 65-84% (P < 0.00001), whereas BNP and CNP decreased DNA synthesis 3% and 12% (both non-significant). Western blots revealed for the first time natriuretic peptide receptors (NPR)-A, -B and -C were present in the renal cancer cells.
  
  
  CONCLUSIONS
  These results indicate that urodilatin and the four cardiac hormones have potent anti-cancer effects by eliminating up to 81% of renal carcinoma cells within 24 h of treatment.
authors.affiliation: James A. Haley Veterans Medical Center and University of South Florida Health Sciences Center, Tampa, 33612, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Vesely
authors.forename: E J
authors.initials: EJ
authors.lastname: Eichelbaum
authors.forename: A A
authors.initials: AA
authors.lastname: Alli
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: W R
authors.initials: WR
authors.lastname: Gower
authors.forename: D L
authors.initials: DL
authors.lastname: Vesely
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use; D010446:Peptide Fragments; D017461:Receptors, Atrial Natriuretic Factor / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor