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Atrial Natriuretic Peptides
  1. David L. Vesely
  1. From the Departments of Internal Medicine, Physiology, and Biophysics, University of South Florida Cardiac Hormone Center, and James A. Haley Veterans' Administration Medical Center, Tampa, FL. Presented in part at the Experimental Biology 2005/XXXV International Congress of Physiological Sciences Meetings, San Diego, CA, March 31-April 6, 2005, in a symposium sponsored by the American Federation of Medical Research and Quest Diagnostics, Inc., entitled “Diagnosis and Treatment Utilizing Natriuretic Peptides.”
  1. Address correspondence to: Dr. David L. Vesely, Cardiac Hormone Center, University of South Florida for Health Sciences, 13000 Bruce B. Downs Blvd, Tampa, FL 33612; e-mail: david.vesely{at}med.va.gov.

Anticancer Agents

Abstract

Atrial natriuretic peptides (ANPs) consist of a family of six peptide hormones that are synthesized by three different genes and then stored as three different prohormones. Within the 126-amino acid ANP prohormone are four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide, and ANP, whose main known biologic properties are blood pressure regulation and maintenance of plasma volume. The newest discovered property of these peptide hormones is their anticancer effects. Vessel dilator, LANP, kaliuretic peptide, and ANP decrease the number of human pancreatic adenocarcinoma cells in culture by 65%, 47%, 37%, and 34%, respectively, within 24 hours at their 1 μM concentrations. Similar results have been found with breast adenocarcinomas, squamous cell lung cancer, and small cell lung cancer cells, each associated with an 83% or greater inhibition of deoxyribonucleic acid (DNA) synthesis by these four peptide hormones. Brain natriuretic peptide has no effects even when increased 100-fold (ie, 100 μM). C-type natriuretic peptide has no effects when increased 10-fold, but when increased 100-fold, it decreases 39% of the cancer cells. At this higher 100 μM concentration, vessel dilator kills 92% of the cancer cells within 24 hours. The four peptide hormones synthesized by the ANP gene given subcutaneously via osmotic pumps in athymic mice with human pancreatic adenocarcinomas completely stop the growth of these adenocarcinomas at 1 week. Vessel dilator, LANP, and kaliuretic peptide within 1 week decrease the volume by 49%, 28%, and 11% of the human pancreatic adenocarcinomas, which, with current anticancer treatment, have a mean survival of only 4 months.

Key Words
  • natriuretic peptides
  • cancer
  • cyclic guanosine monophosphate
  • DNA synthesis

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