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

Vessoni, Alexandre TeixeiraQuinet, AnnabelLima, Leonardo Carmo de AndradeMartins, Davi JardimGarcia, Camila Carrião MachadoRocha, Clarissa Ribeiro ReilyVieira, Debora BragaMenck, Carlos Frederico Martins2016-07-252016-07-252015VESSONI, A. T. et al. Chloroquine - induced glioma cells death is associated with mitochondrial membrane potential loss, but not oxidative stress. Free Radical Biology & Medicine, v. 90, p. 91, 2015. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0891584915011065>. Acesso em: 16 jun. 2016.0891-5849http://www.repositorio.ufop.br/handle/123456789/6621Chloroquine (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 under lying cell death induced by this drug are poorly under stood. Here, we analyzed inatime – anddose – dependent manner, the effects of CQ up on mitochondria integrity, autophagy regulation and redox processes in four human glioma cell lines that differin their resistance to this drug. NAC – containing media protected cells against CQ-induced loss of mitochondrial membrane potential (MMP), autophagyic 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.en-USabertoGliomaGlutathioneMitochondrial membrane potentialOxidative stressAutophagyChloroquine - induced glioma cells death is associated with mitochondrial membrane potential loss, but not oxidative stress.Artigo publicado em periodicoO periódico Free Radical Biology and Medicine concede permissão para depósito deste artigo no Repositório Institucional da UFOP. Número da licença: 3894850581073.https://doi.org/10.1016/j.freeradbiomed.2015.11.008