Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate

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.

Implication of transcriptome profiling of spermatozoa for stallion fertility

“…Myoinositol is distributed in the tissues of many organisms and plays an essential role in the signal transduction system in cells (Condorelli et al 2011). In addition, inositol is involved in several activities and pathways, such as mRNA transcription, cytoskeleton and chromatin remodelling and P53 activity (Bizzarri et al 2016). In conclusion, myoinositol plays a key role in the male reproductive system by regulating the osmolality of the seminal plasma, as well as sperm motility and acrosome reaction (Condorelli et al 2011).…”

Nutraceuticals: Curative Integrative Cancer Treatment

“…Inositols include inositol phophates, inositol hexakisphosphate (InsP6), and myo-Inositol [67]. Cereals, legumes, and oilseeds yield InsP6, which is broken down to myo-Inositol and inositol phosphates [67].…”

“…Inositol hexaphosphate inhibits proliferation [26]. Inositols inhibit cell cycles by inhibiting pRB phosphorylation and increasing pRB/E2F complex formation [67]. Inositols reduce PI3K, disrupt FGF receptor binding and EGF-transduction, down regulate Akt and Erk, inhibit NF-κβ, and decrease COX2 and PGE2 expression [67].…”

“…Inositols inhibit cell cycles by inhibiting pRB phosphorylation and increasing pRB/E2F complex formation [67]. Inositols reduce PI3K, disrupt FGF receptor binding and EGF-transduction, down regulate Akt and Erk, inhibit NF-κβ, and decrease COX2 and PGE2 expression [67]. Inositols impair β-catenin translocation, N-cadherin, Notch-1, SNAI1 release, and Wnt-activation [67].…”

“…Inositols reduce PI3K, disrupt FGF receptor binding and EGF-transduction, down regulate Akt and Erk, inhibit NF-κβ, and decrease COX2 and PGE2 expression [67]. Inositols impair β-catenin translocation, N-cadherin, Notch-1, SNAI1 release, and Wnt-activation [67]. Inositols inhibit MMPs and ROCK1/2 release, decrease cofilin and fascin, upregulate focal adhesion kinase (FAK) and e-cadherin, impairing invasiveness and contributing to cancer microenvironment alterations [67].…”