Cardiac hormones are potent inhibitors of secreted frizzled‑related protein‑3 in human cancer cells
- Authors:
- William P. Skelton
- Michelle Skelton
- David L. Vesely
View Affiliations
Affiliations: Departments of Medicine, Molecular Pharmacology and Physiology, James A. Haley Veterans Administration Medical Center and University of South Florida Morsani Health Sciences Center, Tampa, FL 33612, USA
- Published online on: November 12, 2012 https://doi.org/10.3892/etm.2012.806
-
Pages:
475-478
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Abstract
Secreted frizzled‑related proteins (sFRPs) are secreted glycoproteins involved in neoplastic growth. Four hormones synthesized in the heart, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide (KP) and long‑acting natriuretic peptide (LANP), have anticancer effects both in vitro and in vivo. These heart hormones were evaluated for their ability to inhibit sFRP‑3, which is associated with tumor invasiveness, in human pancreatic cancer, colorectal cancer and renal adenocarcinoma cell lines. Vessel dilator, KP, ANP and LANP maximally reduced the concentration of sFRP‑3 by 83%, 83%, 84% and 83%, respectively (each at P<0.0001), in the human colorectal adenocarcinoma cells. In the human pancreatic carcinoma cells, the concentration of sFRP‑3 was maximally reduced by 77%, 77%, 77% and 78% (each at P<0.0001) secondary to treatment with vessel dilator, KP, ANP and LANP, respectively. In the human renal adenocarcinoma cells, the sFRP‑3 was maximally reduced by vessel dilator, KP, ANP and LANP by 68%, 66%, 68% and 66% (each at P<0.0001), respectively. The results indicate that these four cardiac hormones are significant inhibitors (up to 84%) of sFRP‑3 in a variety of human cancer cells. Furthermore, these data suggest that the metabolic targeting of sFRP‑3 by the cardiac hormones contributes to their anticancer mechanism(s) of action.
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