Cardiac hormones are potent inhibitors of secreted frizzled-related protein-3 in human cancer cells

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 anti-cancer mechanism(s) of action.