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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Atrial Natriuretic Peptide: A Magic Bullet for Cancer Therapy Targeting Wnt Signaling and Cellular pH Regulators

Author(s): A. Serafino and P. Pierimarchi

Volume 21 , Issue 21 , 2014

Page: [2401 - 2409] Pages: 9

DOI: 10.2174/0929867321666140205140152

Abstract

Atrial natriuretic peptide (ANP) is a cardiac hormone playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. In the last years, the new property ascribed to ANP of inhibiting tumor growth both in vitro and in vivo has made this peptide an attractive candidate for anticancer therapy. The molecular mechanism underlying the anti-proliferative effect of ANP has been mainly related to its interaction with the specific receptors NPRs, through which this natriuretic hormone inhibits some metabolic targets critical for cancer development, including the Ras-MEK1⁄2-ERK1⁄2 kinase cascade, functioning as a multikinase inhibitor. In this review we summarize the current knowledge on this topic, focusing on our recent data demonstrating that the antitumor activity of this natriuretic hormone is also mediated by a concomitant effect on the Wnt/β-catenin pathway and on the pH regulation ability of cancer cells, through a Frizzled-related mechanism. This peculiarity of simultaneously targeting two processes crucial for neoplastic transformation and solid tumor survival reinforces the utility of ANP for the development of both preventive and therapeutic strategies.

Keywords: Antitumor effect, atrial natriuretic peptide, cardiac hormones, corin, frizzled, mechanism(s) of action, NHE-1 inhibition, pH regulators, target therapy, tumor microenvironmental pH, Wnt pathway.


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