Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

nhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cell

Texto completo
Autor(es):
Colturato-Kido, Carina [1] ; Lopes, Rayssa M. [1] ; Medeiros, Hyllana C. D. [1] ; Costa, Claudia A. [2] ; Prado-Souza, Laura E. L. [1] ; Ferraz, Leticia S. [1] ; Rodrigues, Tiago [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas CCNH, BR-09210580 Santo Andre, SP - Brazil
[2] Univ Mogi das Cruzes UMC, Ctr Interdisciplinar Invest Bioquim CIIB, BR-08780911 Mogi Das Cruzes, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: LIFE-BASEL; v. 11, n. 4 APR 2021.
Citações Web of Science: 0
Resumo

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells that affects children and adults. Despite the high cure rates, drug resistance still remains a significant clinical problem, which stimulates the development of new therapeutic strategies and drugs to improve the disease outcome. Antipsychotic phenothiazines have emerged as potential candidates to be repositioned as antitumor drugs. It was previously shown that the anti-histaminic phenothiazine derivative promethazine induced autophagy-associated cell death in chronic myeloid leukemia cells, although autophagy can act as a ``double-edged sword{''} contributing to cell survival or cell death. Here we evaluated the role of autophagy in thioridazine (TR)-induced cell death in the human ALL model. TR induced apoptosis in ALL Jurkat cells and it was not cytotoxic to normal peripheral mononuclear blood cells. TR promoted the activation of caspase-8 and -3, which was associated with increased NOXA/MCL-1 ratio and autophagy triggering. AMPK/PI3K/AKT/mTOR and MAPK/ERK pathways are involved in TR-induced cell death. The inhibition of the autophagic process enhanced the cytotoxicity of TR in Jurkat cells, highlighting autophagy as a targetable process for drug development purposes in ALL. (AU)

Processo FAPESP: 16/07367-5 - Investigação dos Mecanismos de Indução de Morte Celular por Fenotiazinas em Células Tumorais: Modulação da Expressão Gênica e Papel das Proteínas da Família BCL-2 e Estresse do Retículo Endoplasmático
Beneficiário:Tiago Rodrigues
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/25747-5 - Alterações de morfologia e dinâmica mitocondriais no câncer: compreensão da biologia tumoral e prospecção de novos alvos terapêuticos
Beneficiário:Tiago Rodrigues
Linha de fomento: Auxílio à Pesquisa - Regular