Novel therapeutic approach for cancer using four cardiovascular hormones.
BACKGROUND
The atrial natriuretic peptide (ANP) gene synthesizes four cardiovascular hormones, i.e. vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and ANP, which decrease the number of human pancreatic adenocarcinoma cells in culture by 65%, 47%, 37%, and 34%, respectively.


METHODS
None of the cardiovascular hormones has been investigated to determine whether they inhibit the growth of cancers in vivo. These four hormones were evaluated for their ability to inhibit the growth of human pancreatic adenocarcinomas in athymic mice.


RESULTS
Vessel dilator (139 ng min(-1) kg(-1) of body weight) infused for 14 days completely stopped the growth of human pancreatic adenocarcinomas in athymic mice (n = 14) with a decrease in their tumour volume, while the tumour volume increased 69-fold (P < 0.001) in the placebo (n = 30)-treated mice. When these peptide hormones (each at 1.4 microg min(-1) kg(-1) body weight) were infused for 4 weeks, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide decreased tumour volume after 1 week by 49%, 28%, and 11%, respectively, with a one- and 20-fold increase in the tumour volume in ANP- and placebo-treated mice. Cyclic GMP (2.4 microg min(-1) kg(-1) body weight) inhibited after 1 week the growth of this cancer 95%.


CONCLUSIONS
These results suggest that these peptide hormones have useful anticancer properties, as they each inhibited the growth of the human pancreatic adenocarcinomas in vivo and three of the four peptide hormones decreased the volume of the tumours (up to 49%, i.e. vessel dilator). Part of their mechanism of action appears to be mediated by cyclic GMP.
University of South Florida Cardiac Hormone Center, Tampa, FL 33612, USA. david.vesely@med.va.gov
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D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D045265:Natriuretic Peptides / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000627:therapeutic use; D011498:Protein Precursors / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor