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Type: Artigo de periódico
Title: Molecular Effects Of The Phosphatidylinositol-3-kinase Inhibitor Nvp-bkm120 On T And B-cell Acute Lymphoblastic Leukaemia.
Author: Pereira, João Kleber Novais
Machado-Neto, João Agostinho
Lopes, Matheus Rodrigues
Morini, Beatriz Corey
Traina, Fabiola
Costa, Fernando Ferreira
Saad, Sara Teresinha Olalla
Favaro, Patricia
Abstract: Constitutive activation of the PI3K pathway in T cell acute lymphoblastic leukaemia (T-ALL) has been reported and in a mouse model, PI3K activation, together with MYC, cooperates in Burkitt lymphoma (BL) pathogenesis. We investigated the effects of NVP-BKM120, a potent pan-class I PI3K inhibitor, in lymphoblastic leukaemia cell lines. Effects of NVP-BKM120 on cell viability, clonogenicity, apoptosis, cell cycle, cell signalling and autophagy were assessed in vitro on T-ALL (Jurkat and MOLT-4) and BL (Daudi and NAMALWA) cell lines. NVP-BKM120 treatment decreased cell viability and clonogenic growth in all tested cells. Moreover, the drug arrested cell cycling in association with a decrease in Cyclin B1 protein levels, and increased apoptosis. Immunoblotting analysis of cells treated with the drug revealed decreased phosphorylation, in a dose-dependent manner, of AKT, mTOR, P70S6K and 4EBP1, with stable total protein levels. Additionally, we observed a dose-dependent decrease in BAD phosphorylation, in association with augmented BAX:BCL2 ratio. Quantification of autophagy showed a dose-dependent increase in acidic vesicular organelles in all cells tested. In summary, our present study establishes that NVP-BKM120 presents an effective antitumour activity against T-ALL and BL cell lines.
Subject: Daudi
Pi3k Pathway
Citation: European Journal Of Cancer (oxford, England : 1990). v. 51, n. 14, p. 2076-2085, 2015-Sep.
Rights: embargo
Identifier DOI: 10.1016/j.ejca.2015.07.018
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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