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Cardiac and renal hormones: anticancer effects in vitro and in vivo

David L Vesely1

  • 1Department of Medicine, Cardiac Hormone Center, University of South Florida Health Sciences Center and James A Haley Veterans Medical Center, Tampa, FL, USA. david.vesely@va.gov

Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research
|December 19, 2008
PubMed
Abstract

Insights

Four cardiovascular hormones demonstrate significant anticancer effects, reducing tumor volume and eliminating up to 80% of pancreatic and two-thirds of breast cancers in mice. These hormones inhibit cancer cell growth and DNA synthesis.

Area of Science:

  • Cardiovascular Endocrinology
  • Cancer Biology
  • Pharmacology

Background:

  • Four cardiovascular hormones exhibit potent cytotoxic effects against various human adenocarcinoma and lung cancer cell lines in vitro.
  • These hormones, including vessel dilator, long-acting natriuretic peptide, kaliuretic peptide, and atrial natriuretic peptide, reduced cancer cell viability by up to 97% within 24 hours at 1 mmol/L.

Purpose of the Study:

  • To investigate the in vivo efficacy of cardiovascular hormones as a potential anticancer therapy.
  • To evaluate the impact of vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide on established human tumor xenografts in athymic mice.

Main Methods:

  • In vivo studies were conducted using athymic mouse models bearing human pancreatic and breast adenocarcinomas.
  • Cardiovascular hormones were administered via subcutaneous osmotic pumps over a period of 1 month.
  • Tumor growth inhibition, volume reduction, and elimination rates were assessed. Cancer cell receptor expression (natriuretic peptide receptors A, B, and C) was noted.

Main Results:

  • Vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide completely halted pancreatic adenocarcinoma growth in mice, reducing tumor volume by 49%, 28%, and 11% respectively within 1 week.
  • Subcutaneous administration for 1 month led to complete elimination of up to 80% of human pancreatic adenocarcinomas and two-thirds of human breast cancers.
  • Atrial natriuretic peptide's effects were mediated by natriuretic peptide receptors A, B, and C present on cancer cells.

Conclusions:

  • Cardiovascular hormones possess significant anticancer properties, effectively reducing tumor burden and eliminating cancers in vivo.
  • The anticancer mechanism involves potent inhibition of mitogen-activated and basal extracellular signal-regulated kinases (ERK 1/2) and MEK 1/2 phosphorylation.
  • These hormones also inhibit DNA synthesis by 80-90%, localizing to the cancer cell nucleus.

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