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.

Broad spectrum anticancer activity of myo-inositol and inositol hexakisphosphate / Bizzarri, Mariano; Dinicola, Simona; Bevilacqua, Arturo; Cucina, Alessandra. - In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY. - ISSN 1687-8337. - STAMPA. - 2016:(2016), pp. 1-14. [10.1155/2016/5616807]

Broad spectrum anticancer activity of myo-inositol and inositol hexakisphosphate

BIZZARRI, Mariano;BEVILACQUA, Arturo;CUCINA, Alessandra
2016

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.
2016
Endocrinology, Diabetes and Metabolism; Endocrinology; Endocrine and Autonomic Systems
01 Pubblicazione su rivista::01a Articolo in rivista
Broad spectrum anticancer activity of myo-inositol and inositol hexakisphosphate / Bizzarri, Mariano; Dinicola, Simona; Bevilacqua, Arturo; Cucina, Alessandra. - In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY. - ISSN 1687-8337. - STAMPA. - 2016:(2016), pp. 1-14. [10.1155/2016/5616807]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/944620
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