Cardiac hormones for the treatment of cancer

    1. David L Vesely
    1. Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine, Molecular Pharmacology and Physiology, James A. Haley VA Medical Center-151, University of South Florida Cardiac Hormone Center, and University of South Florida Morsani School of Medicine, 13000 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA
    1. (Correspondence should be addressed to D L Vesely; Email: david.vesely{at}


    Four cardiac hormones, namely atrial natriuretic peptide, vessel dilator, kaliuretic peptide, and long-acting natriuretic peptide, reduce up to 97% of all cancer cells in vitro. These four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas, two-thirds of human breast cancers, and up to 80% of human pancreatic adenocarcinomas growing in athymic mice. Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the rat sarcoma-bound GTP (RAS) (95% inhibition)–mitogen-activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)–extracellular signal-related kinase 1/2 (ERK 1/2) (96% inhibition) cascade in cancer cells. They also inhibit MAPK9, i.e. c-Jun N-terminal kinase 2. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%). One of the downstream targets of VEGF is β-catenin, which they reduce up to 88%. The WNT pathway is inhibited up to 68% and secreted frizzled-related protein 3 decreased up to 84% by the four cardiac hormones. AKT, a serine/threonine protein kinase, is reduced up to 64% by the cardiac hormones. STAT3, a final ‘switch’ that activates gene expression that leads to malignancy, is decreased by up to 88% by the cardiac hormones. STAT3 is specifically decreased as they do not affect STAT1. There is a cross-talk between the RAS–MEK 1/2–ERK 1/2 kinase cascade, VEGF, β-catenin, WNT, JNK, and STAT pathways and each of these pathways is inhibited by the cardiac hormones.

    • Revision received 21 March 2013
    • Accepted 25 March 2013
    • Made available online as an Accepted Preprint 26 March 2013
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