Atrial Natriuretic Peptide: A Magic Bullet for Cancer Therapy Targeting Wnt Signaling and Cellular pH Regulators
A. Serafino and P. Pierimarchi
Affiliation: Institute of Translational Pharmacology - National Research Council of Italy, Via Fosso del Cavaliere 100, 00133, Rome, Italy.
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.
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.
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