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Natriuretic Peptides’ Metabolic Targets for Treatment of Cancer
  1. David L. Vesely, MD, PhD, FACP, FACE*†
  1. From the *Division of Endocrinology, Diabetes and Metabolism and †Departments of Medicine, Molecular Pharmacology, and Physiology, James A. Haley VA Medical Center and University of South Florida Cardiac Hormone Center, and University of South Florida Morsani School of Medicine, Tampa, FL.
  1. Received February 21, 2013, and in revised form March 20, 2013.
  2. Accepted for publication March 10, 2013.
  3. Reprints: David L. Vesely, MD, PhD, FACP, FACE, USF Cardiac Hormone Center, University of South Florida Morsani School of Medicine, Tampa, FL; J A Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd, Tampa, FL. E-mail: david.vesely{at}va.gov.
  4. This work was supported in part by Merit Review Grants from the United States Department of Veterans Affairs, the James and Esther King Florida Biomedical Research Program, the Florida Department of Health, and the Mama Mare Breast Cancer Foundation. The contents of this article do not represent the views of the Department of Veterans Affairs or of the United States Government.
  5. The patent to treat cancer with these cardiac hormones has been assigned to the University of South Florida, which has not licensed this patent to any commercial entity. There has been no pharmaceutical company funding or input into the studies described herein.

Abstract

Four cardiac hormones are synthesized by the atrial natriuretic peptide prohormone gene. These hormones, namely, long-acting natriuretic peptide, vessel dilator, kaliuretic peptide, and atrial natriuretic peptide, help regulate blood pressure and blood volume by causing vasodilation, diuresis, and sodium excretion. These cardiac hormones reduce up to 97% of all cancer cells in vitro. These 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 guanosine diphosphate conversion to RAS guanosine triphosphate (95% inhibition)–mitogen-activated protein kinase kinase 1/2 (98% inhibition)–extracellular signal-related kinase 1/2 (96% inhibition) cascade in cancer cells. They also reduce c-Jun-N-terminal kinase 2 up to 89%. These multiple kinase inhibitors are also inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89% inhibition). They reduce β-catenin up to 88%. They inhibit the WNT pathway up to 68%, and secreted Frizzled-related protein 3 is decreased up to 84%. AKT, a serine/threonine-protein kinase, is reduced up to 64% by the cardiac hormones. Signal transducer and activator of transcription 3, a final “switch” that activates gene expression that leads to malignancy, is decreased by up to 88% by the cardiac hormones. Of importance, the cross talk between the multiple kinases, VEGF, B-catenin, WNT, and STAT pathways is inhibited by the 4 cardiac hormones.

Key Words
  • cardiac hormones
  • RAS-MEK 1/2-ERK-1/2- kinase cascade
  • signal transducer and activator of transcription 3
  • vascular endothelial growth factor
  • β-catenin

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