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

Alexandre Teixeira Vessoni, Annabel Quinet, Leonardo Carmo De Andrade-Lima, Davi Jardim Martins, Camila Carrião Machado Garcia, Clarissa Ribeiro Reily Rocha, Debora Braga Vieira, Carlos Frederico Martins Menck

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalFree Radical Biology and Medicine
Volume90
DOIs
StatePublished - Jan 1 2016

Keywords

  • Autophagy
  • Chloroquine
  • Glioma
  • Glutathione
  • Mitochondrial membrane potential
  • Oxidative stress

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