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Atrial natriuretic peptide and long-acting natriuretic peptide inhibit ras in human prostate cancer cells

Ying Sun1, Ehrentraud J Eichelbaum, Anne Lenz

  • 1Department of Internal Medicine, University of South Florida Cardiac Hormone Center, and James A. Haley Veterans Medical Center-151, Tampa, Florida 33612, U.S.A.

Anticancer Research
|June 17, 2009
PubMed
Abstract

Insights

Atrial natriuretic peptide and long-acting natriuretic peptide demonstrate anticancer effects by inhibiting Ras activation in prostate cancer cells. This inhibition is partly mediated by cyclic GMP, revealing a key anticancer mechanism.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Atrial natriuretic peptide (ANP) and long-acting natriuretic peptide (LANP) exhibit anticancer properties in human prostate adenocarcinoma.
  • The Ras signaling pathway is frequently dysregulated in cancer, making it a target for therapeutic intervention.

Purpose of the Study:

  • To investigate the effects of ANP and LANP on Ras activation in human prostate adenocarcinoma cells.
  • To elucidate the role of cyclic GMP (cGMP) in the mechanism of action of ANP and LANP.

Main Methods:

  • Human prostate adenocarcinoma cells were treated with varying concentrations of ANP and LANP.
  • The activation status of Ras (Ras-GTP) and phosphorylation of Ras were measured.
  • The influence of cyclic GMP (cGMP) and cGMP antibodies on these processes was assessed.

Main Results:

  • ANP and LANP significantly reduced Ras-GTP levels in a dose-dependent manner (0.01 microM to 1 microM).
  • Both peptides inhibited Ras phosphorylation by over 80% at 0.1 microM, with effects lasting up to 24 hours.
  • Cyclic GMP was shown to mediate the inhibitory effects of ANP and LANP on Ras, as evidenced by inhibition with cGMP antibodies and direct inhibition by cGMP.

Conclusions:

  • ANP and LANP possess anticancer activity against prostate adenocarcinoma by inhibiting Ras signaling.
  • The anticancer effects of these natriuretic peptides are, in part, mediated through a cyclic GMP-dependent pathway.
  • These findings highlight a novel therapeutic strategy targeting Ras via natriuretic peptides in prostate cancer.

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