New anticancer agents: hormones made within the heart

Anticancer Res. 2012 Jul;32(7):2515-21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Atrial Natriuretic Factor / pharmacology
  • Humans
  • Myocardium / chemistry*
  • Myocardium / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Hormones / pharmacology*
  • Protein Precursors / pharmacology

Substances

  • Antineoplastic Agents
  • Peptide Fragments
  • Peptide Hormones
  • Protein Precursors
  • atrial natriuretic factor precursor (79-98)
  • atrial natriuretic factor prohormone (1-30), human
  • atrial natriuretic factor prohormone (31-67)
  • Atrial Natriuretic Factor