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Myoinositol and Inositol Hexakisphosphate in the Treatment of Breast Cancer: Molecular Mechanisms

  • Mariano BizzarriEmail author
  • Simona Dinicola
  • Alessandra Cucina
Chapter
Part of the ISGE Series book series (ISGE)

Abstract

Studies on myoinositol (Myo-Ins) and its main phosphate derivative—inositol hexakisphosphate (InsP6)—are gaining momentum given the critical role they play in a number of diseases, including cancer. Namely, in breast tumors, inositol content and metabolism have been demonstrated to be significantly deregulated. On the other hand, inositol supplementation reduces cell growth by inhibiting pRB phosphorylation and consequently the pRB/E2F complexes formation, a key step during cell cycle progression. Inositols severely decrease 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 weakened upon inositol addition. Downregulation of both Akt and ERK leads consequently to NF-κB inhibition and reduced expression of inflammatory markers, like 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 directly with different cytoskeleton components, by upregulating focal adhesion kinase and E-cadherin, and decreasing fascin and cofilin, leading hence to invasiveness inhibition. The inositol-induced impairment of both metalloproteinases and ROCK1/2 release further reinforces the negative modulation on cell motility. Overall, these effects enable inositols in remodeling the cytoskeleton architecture and the cell-microenvironment interplay.

Keywords

Myoinositol Inositol hexakisphosphate Breast cancer Cytoskeleton Tumor microenvironment 

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Copyright information

© International Society of Gynecological Endocrinology 2018

Authors and Affiliations

  • Mariano Bizzarri
    • 1
    Email author
  • Simona Dinicola
    • 1
    • 2
  • Alessandra Cucina
    • 2
    • 3
  1. 1.Department of Experimental MedicineSapienza University of RomeRomeItaly
  2. 2.Department of Surgery “Pietro Valdoni”Sapienza University of RomeRomeItaly
  3. 3.Azienda Policlinico Umberto IRomeItaly

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