Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 1997 Jul 15;57(14):2873-8.

Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3' kinase.

Author information

1
The Hormel Institute, University of Minnesota, Austin 55912, USA.

Erratum in

  • Cancer Res 1997 Nov 15;57(22):5198.

Abstract

Inositol hexaphosphate (InsP6) is the most abundant inositol phosphate found in plants. In mammalian cells, the concentrations of InsP6 are between 10 and 100 microM. Previous work has indicated that InsP6 is an effective cancer chemopreventive and chemotherapeutic agent. However, the molecular mechanisms involved in the inhibition of carcinogenesis by InsP6 remain unclear. In this study, we investigated the influence of InsP6 on tumor promoter-induced cell transformation and signal transduction pathways leading to activator protein 1 activation, which is considered to play a crucial role in tumor promotion. InsP6 markedly blocks epidermal growth factor-induced phosphatidylinositol-3 (PI-3) kinase activity in a dose-dependent manner in JB6 cells and directly in vitro. Blocking PI-3 kinase activity by InsP6 profoundly impairs epidermal growth factor- or phorbol ester-induced JB6 cell transformation and extracellular signal-regulated protein kinases activation, as well as activator protein 1 activation. These results provide the first evidence that the molecular mechanism of InsP6 antitumor promotion effect targets and blocks PI-3 kinase activation and demonstrate that PI-3 kinase can serve as a molecular target for the development of cancer chemopreventive agents.

PMID:
9230193
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center