Novel therapeutic approach for cancer using four cardiovascular hormones
D L Vesely1, L C Clark, A H Garces
1University of South Florida Cardiac Hormone Center, Tampa, FL 33612, USA. david.vesely@med.va.gov
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 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.
Insights
Cardiovascular hormones, including vessel dilator, inhibit pancreatic cancer growth in vivo. Vessel dilator completely stopped tumor growth, and cyclic GMP showed significant anticancer effects, suggesting therapeutic potential.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- The atrial natriuretic peptide (ANP) gene encodes four cardiovascular hormones with known in vitro effects on pancreatic cancer cells.
- These hormones include vessel dilator, long-acting natriuretic peptide, kaliuretic peptide, and ANP.
Purpose of the Study:
- To investigate the in vivo efficacy of these four cardiovascular hormones in inhibiting human pancreatic adenocarcinoma growth.
- To evaluate the potential anticancer properties of these peptide hormones in an animal model.
Main Methods:
- Human pancreatic adenocarcinomas were implanted in athymic mice.
- Mice were treated with infusions of vessel dilator, long-acting natriuretic peptide, kaliuretic peptide, ANP, or placebo.
- Cyclic GMP was also administered to assess its effect on tumor growth.
Main Results:
- Vessel dilator infusion completely halted tumor growth and reduced tumor volume in mice.
- Long-acting natriuretic peptide and kaliuretic peptide significantly decreased tumor volume, while ANP showed minimal effect.
- Cyclic GMP demonstrated a 95% inhibition of cancer growth after one week.
Conclusions:
- The studied peptide hormones exhibit anticancer properties against human pancreatic adenocarcinomas in vivo.
- Vessel dilator and cyclic GMP show significant potential for therapeutic applications in pancreatic cancer.
- Cyclic GMP appears to mediate, at least in part, the anticancer mechanism of these hormones.
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