Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/235552
Type: Artigo
Title: Molecular effects of the phosphatidylinositol-3-kinase inhibitor nvp-bkm120 on t and b-cell acute lymphoblastic leukaemia
Author: Pereira, J.K.N.
Machado, J.A.N.
Lopes, M.R.
Morini, B.C.
Traina, F.
Costa, F.F.
Saad, S.T.O.
Favaro, P.
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.
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-BK
Subject: Apoptose
Autofagia
Sobrevivência celular
Terapia de alvo molecular
Country: Inglaterra
Editor: Elsevier
Citation: European Journal Of Cancer (oxford, England : 1990). v. 51, n. 14, p. 2076-2085, 2015-Sep.
Rights: fechado
Identifier DOI: 10.1016/j.ejca.2015.07.018
Address: https://www.sciencedirect.com/science/article/pii/S095980491500698X
Date Issue: 2015
Appears in Collections:FCM - Artigos e Outros Documentos

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