Combined SRPK and AKT pharmacological inhibition is synergistic in T-cell acute lymphoblastic leukemia cells.

Autor: Siqueira RP; Universidade Federal de Viçosa, Departamento de Bioquímica e Biologia Molecular, Viçosa, MG, Brazil. Electronic address: raoni.siqueira1@gmail.com., Caetano MMM; Universidade Federal de Viçosa, Departamento de Bioquímica e Biologia Molecular, Viçosa, MG, Brazil., de Souza LÂ; Universidade Federal de Viçosa, Departamento de Biologia Geral, Viçosa, MG, Brazil., Dos Passos PMS; Universidade Federal de São Carlos, Departamento de Genética e Evolução, São Carlos, SP, Brazil., Simaroli NB; Universidade Federal de São Carlos, Departamento de Genética e Evolução, São Carlos, SP, Brazil., Barros MVA; Universidade Federal de Viçosa, Departamento de Química, Viçosa, MG, Brazil., de Souza APM; Universidade Federal de Viçosa, Departamento de Química, Viçosa, MG, Brazil., de Oliveira LL; Universidade Federal de Viçosa, Departamento de Biologia Geral, Viçosa, MG, Brazil., Silva-Júnior A; Universidade Federal de Viçosa, Departamento de Veterinária, Viçosa, MG, Brazil., Fietto JLR; Universidade Federal de Viçosa, Departamento de Bioquímica e Biologia Molecular, Viçosa, MG, Brazil., Teixeira RR; Universidade Federal de Viçosa, Departamento de Química, Viçosa, MG, Brazil., Teixeira FR; Universidade Federal de São Carlos, Departamento de Genética e Evolução, São Carlos, SP, Brazil., Bressan GC; Universidade Federal de Viçosa, Departamento de Bioquímica e Biologia Molecular, Viçosa, MG, Brazil. Electronic address: gustavo.bressan@ufv.br.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2020 Jun; Vol. 65, pp. 104777. Date of Electronic Publication: 2020 Jan 18.
DOI: 10.1016/j.tiv.2020.104777
Abstrakt: The serine/arginine protein kinases respond to the EGFR-PI3K-AKT signaling module in the context of pre-mRNA alternative splicing regulation. These enzymes (notably SRPK1 and SRPK2) have been found dysregulated in a variety of cancers, which suggests them as promising drug targets in oncology. SRPK2 has been related to leukemia cells proliferation and found preferentially overexpressed in T-cell acute lymphoblastic leukemia (T-ALL). Previously, synergistic combination between vincristine and SRPK inhibitors has been observed in leukemia cells in vitro. Herein we sought to evaluate the in vitro combinatory effects of inhibiting SRPK and multiple other kinase targets from the EGFR pathway in T-ALL, a hematological malignancy with a still poor prognosis. We found that the combined SRPK and AKT pharmacological inhibition is synergistic in Jurkat, CCRF-CEM, and TALL-1 (all T-ALL) but not in HL60, an acute myelogenous leukemia cell lineage. Combined treatments also impaired SR proteins phosphorylation in accordance with an improved suppression of SRPK activity. Furthermore, the synergism of treatments seemed associated with apoptosis triggering, as revealed by flow cytometry analyses. Taken together, these results suggest the therapeutic potential of the combined SRPK and AKT pharmacological inhibition against T-ALL.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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