Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway

Enza Piccolo, Sara Vignati, Tania Maffucci, Pasquale F. Innominato, Andrew M. Riley, Barry V L Potter, Pier Paolo Pandolfi, Massimo Broggini, Stefano Iacobelli, Paolo Innocenti, Marco Falasca

Research output: Contribution to journalArticle

Abstract

Phosphoinositide 3-kinase (PI 3-K) is implicated in a wide array of biological and pathophysiological responses, including tumorigenesis, invasion and metastasis, therefore specific inhibitors of the kinase may prove useful in cancer therapy. We propose that specific inositol polyphosphates have the potential to antagonize the activation of PI 3-K pathways by competing with the binding of PtdIns(3,4,5)P3 to pleckstrin homology (PH) domains. Here we show that Ins(1,3,4,5,6)P5 inhibits the serine phosphorylation and the kinase activity of Akt/PKB. As a consequence of this inhibition, Ins(1,3,4,5,6)P5 induces apoptosis in ovarian, lung and breast cancer cells. Overexpression of constitutively active Akt protects SKBR-3 cells from Ins(1,3,4,5,6)P5-induced apoptosis. Furthermore, Ins(1,3,4,5,6)P5 enhances the proapoptotic effect of cisplatin and etoposide in ovarian and lung cancer cells, respectively. These results support a role for Ins(1,3,4,5,6)P5 as a specific inhibitor of the PI 3-K/ Akt signalling pathway, that may sensitize cancer cells to the action of commonly used anticancer drugs.

Original languageEnglish
Pages (from-to)1754-1765
Number of pages12
JournalOncogene
Volume23
Issue number9
DOIs
Publication statusPublished - Mar 4 2004

Keywords

  • Apoptosis
  • Inositol polyphosphates
  • Phosphoinositide 3-kinase
  • Pleckstrin homology domain
  • Protein kinase B-Akt

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway'. Together they form a unique fingerprint.

  • Cite this

    Piccolo, E., Vignati, S., Maffucci, T., Innominato, P. F., Riley, A. M., Potter, B. V. L., Pandolfi, P. P., Broggini, M., Iacobelli, S., Innocenti, P., & Falasca, M. (2004). Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway. Oncogene, 23(9), 1754-1765. https://doi.org/10.1038/sj.onc.1207296