title: Cardiac hormones for the treatment of cancer.
abstract: 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.
authors.affiliation: 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, Tampa, Florida 33612, USA. david.vesely@va.gov
authors.forename: David L
authors.initials: DL
authors.lastname: Vesely
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D036361:Peptide Hormones
keywords: RAS; cancer; hormones; β-catenin