Chloroquine-induced glioma cells death is associated with mitochondrial membrane potential loss, but not oxidative stress

Author(s)

Vessoni, Alexandre Teixeira ^[1] ; Quinet, Annabel ^[1] ; de Andrade-Lima, Leonardo Carmo ^[1] ; Martins, Davi Jardim ^[1] ; Machado Garcia, Camila Carriao ^{[2, 3]} ; Reily Rocha, Clarissa Ribeiro ^[1] ; Vieira, Debora Braga ^[1] ; Martins Menck, Carlos Frederico ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Ouro Preto, Inst Ciencias Exatas & Biol, Nucleo Pesquisa Ciencias Biol, BR-35400000 Minas Gerais, MG - Brazil

^[3] Univ Fed Ouro Preto, Inst Ciencias Exatas & Biol, Dept Ciencias Biol, BR-35400000 Minas Gerais, MG - Brazil

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 90, p. 91-100, JAN 2016.
• Web of Science Citations: 9

Abstract

Chloroquine (CQ), a quinolone derivative widely used to treat and prevent malaria, has been shown to exert a potent adjuvant effect when combined with conventional glioblastoma therapy. Despite inducing lysosome destabilization and activating p53 in human glioma cells, the mechanisms underlying cell death induced by this drug are poorly understood. Here, we analyzed in a time- and dose-dependent manner, the effects of CQ upon mitochondria integrity, autophagy regulation and redox processes in four human glioma cell lines that differ in their resistance to this drug. NAC-containing media protected cells against CQ-induced loss of mitochondrial membrane potential (MMP), autophagic vacuoles (LC3II) accumulation and loss of cell viability induced by CQ. However, we noticed that part of this protection was due to media acidification in NAC preparations, alerting for problems in experimental procedures using NAC. The results indicate that although CQ induces accumulation of LC3II, mitochondria, and oxidative stress, neither of these events is clearly correlated to cell death induced by this drug. The only event elicited in all cell lines at equitoxic doses of CQ was the loss of MMP, indicating that mitochondrial stability is important for cells resistance to this drug. Finally, the data indicate that higher steady-state MMP values can predict cell resistance to CQ treatment. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants