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International Journal of Endocrinology
Volume 2016, Article ID 5616807, 14 pages
http://dx.doi.org/10.1155/2016/5616807
Review Article

Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate

1Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
2Systems Biology Group Lab, Sapienza University of Rome, Rome, Italy
3Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy
4Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy
5Department of Psychology, Section of Neuroscience, Sapienza University of Rome, Via dei Marsi 78, 00185 Rome, Italy
6Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy

Received 6 July 2016; Accepted 6 September 2016

Academic Editor: John E. Nestler

Copyright © 2016 Mariano Bizzarri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation. Upstream of that pathway, inositols disrupt the ligand interaction between FGF and its receptor as well as with the EGF-transduction processes involving IGF-II receptor and AP-1 complexes. Additionally, Akt activation is severely impaired upon inositol addition. Downregulation of both Akt and ERK leads consequently to NF-kB inhibition and reduced expression of inflammatory markers (COX-2 and PGE2). Remarkably, inositol-induced downregulation of presenilin-1 interferes with the epithelial-mesenchymal transition and reduces Wnt-activation, β-catenin translocation, Notch-1, N-cadherin, and SNAI1 release. Inositols interfere also with the cytoskeleton by upregulating Focal Adhesion Kinase and E-cadherin and decreasing Fascin and Cofilin, two main components of pseudopodia, leading hence to invasiveness impairment. This effect is reinforced by the inositol-induced inhibition on metalloproteinases and ROCK1/2 release. Overall, these effects enable inositols to remodel the cytoskeleton architecture.