D-pinitol inhibits prostate cancer metastasis through inhibition of αVβ3 integrin by modulating FAK, c-Src and NF-κB pathways

Int J Mol Sci. 2013 May 8;14(5):9790-802. doi: 10.3390/ijms14059790.

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • CSK Tyrosine-Protein Kinase
  • Cell Line, Tumor
  • Focal Adhesion Kinase 1 / immunology
  • Humans
  • Inositol / analogs & derivatives*
  • Inositol / pharmacology
  • Integrin alphaVbeta3 / immunology
  • Male
  • NF-kappa B / immunology
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / pathology
  • Prostate / drug effects*
  • Prostate / immunology
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology*
  • Signal Transduction / drug effects*
  • src-Family Kinases / immunology

Substances

  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • NF-kappa B
  • pinitol
  • Inositol
  • CSK Tyrosine-Protein Kinase
  • Focal Adhesion Kinase 1
  • src-Family Kinases
  • CSK protein, human