Novel therapeutic approach for cancer using four cardiovascular hormones

Authors

  • D. L. Vesely,

    Corresponding author
    1. University of South Florida Cardiac Hormone Center, and
    2. James A. Haley Veterans Medical Center, Tampa, FL, USA
      David L. Vesely, Professor of Medicine, Physiology & Biophysics, Director, USF Cardiac Hormone Center, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel.: (813) 972–7624; fax: (813) 972 7623; e-mail: david.vesely@med.va.gov
    Search for more papers by this author
  • L. C. Clark,

    1. University of South Florida Cardiac Hormone Center, and
    2. James A. Haley Veterans Medical Center, Tampa, FL, USA
    Search for more papers by this author
  • A. H. Garces,

    1. University of South Florida Cardiac Hormone Center, and
    2. James A. Haley Veterans Medical Center, Tampa, FL, USA
    Search for more papers by this author
  • Q. W. McAfee,

    1. University of South Florida Cardiac Hormone Center, and
    2. James A. Haley Veterans Medical Center, Tampa, FL, USA
    Search for more papers by this author
  • J. Soto,

    1. James A. Haley Veterans Medical Center, Tampa, FL, USA
    Search for more papers by this author
  • W. R. Gower Jr

    1. University of South Florida Cardiac Hormone Center, and
    2. James A. Haley Veterans Medical Center, Tampa, FL, USA
    Search for more papers by this author

  • Departments of Internal Medicine (D. L. Vesely, L. C. Clark, A. H. Garces, J. Soto), Biochemistry and Molecular Biology (Q. W. McAfee, W. R. Gower Jr), and Physiology and Biophysics (D. L. Vesely, W. R. Gower Jr), University of South Florida Cardiac Hormone Center; James A. Haley Veterans Medical Center (D. L. Vesely, L. C. Clark, A. H. Garces, Q. W. McAfee, J. Soto, W. R. Gower Jr), Tampa, FL, USA.

David L. Vesely, Professor of Medicine, Physiology & Biophysics, Director, USF Cardiac Hormone Center, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel.: (813) 972–7624; fax: (813) 972 7623; e-mail: david.vesely@med.va.gov

Abstract

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 and materials  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 µg 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 µg 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.

Ancillary