title: New anticancer agents: hormones made within the heart.
abstract: The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide (ANP) prohormone which contains four peptide hormones, namely atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas, as well as small-cell and squamous cell lung cancer cells within 24 hours in cell culture. In vivo these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, up to two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers in athymic mice. Their anticancer mechanism(s) target the Rat sarcoma bound guanosine triphosphate (RAS)-mitogen activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal related kinase 1/2 (ERK1/2) kinase cascade in cancer cells. These four cardiac hormones inhibit up to 95% of the basal activity of Ras, 98% of the phosphorylation of MEK1/2 kinases and 96% of the activation of basal activity of ERK1/2 kinases. They also completely block the activity of mitogens such as the ability of epidermal growth factor to stimulate ERK and RAS. In addition to inhibiting these mitogen-activated protein kinases (MAPKs) they also inhibit MAPK9, i.e. c-Jun-N-terminal kinase 2. These multiple kinase inhibitors are cytotoxic and cause cell death of cancer cells but not of normal cells.
authors: Department of Medicine, James A. Haley Veterans Hospital (151), 13000 Bruce B. Downs Blvd., Tampa, Florida 33612, USA. david.vesely@va.gov
authors: David L
authors: DL
authors: Vesely
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006801:Humans; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D036361:Peptide Hormones; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor