Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth and Proliferation in Mantle Cell Lymphoma

  • Andreeff, Raffeld
  • Published 2013

Abstract

Background/Aims: Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway preferentially occurs in aggressive blastoid variants of mantle cell lymphoma (MCL) and is implicated in the pathogenesis of this disease. In this study, we investigated the role of PI3K isoforms on proliferation of aggressive MCL cells. Methods: The changes in cell viability, cell cycle distribution and apoptosis induction by the PI3K isoform-selective inhibitors were evaluated. The molecular basis underlying the effects of the specific inhibition of PI3K isoforms was investigated by Western blot analysis. Results: Our results demonstrated that a class IA PI3K isoform is most commonly involved in the constitutive activation of Akt in aggressive MCL. Treatment with a p110α isoform-specific inhibitor induced prominent cell cycle arrest followed by apoptosis through complete abolishment of phosphorylated (p)-Akt and its downstream targets. An inhibitor of isoform p110δ induced moderate cell cycle arrest with downReceived: November 21, 2012 Accepted after revision: May 7, 2013 Published online: September 19, 2013 Yoko Tabe, MD, PhD Department of Clinical Laboratory Medicine Juntendo University School of Medicine 2-1-1 Bunkyo-ku, Hongo, Tokyo (Japan) E-Mail tabe @ juntendo.ac.jp © 2013 S. Karger AG, Basel 0001–5792/14/1311–0059$39.50/0

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Cite this paper

@inproceedings{Andreeff2013ClassIP, title={Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth and Proliferation in Mantle Cell Lymphoma}, author={Andreeff and Raffeld}, year={2013} }