TY - JOUR
T1 - Chloroquine-induced glioma cells death is associated with mitochondrial membrane potential loss, but not oxidative stress
AU - Vessoni, Alexandre Teixeira
AU - Quinet, Annabel
AU - Andrade-Lima, Leonardo Carmo De
AU - Martins, Davi Jardim
AU - Garcia, Camila Carrião Machado
AU - Rocha, Clarissa Ribeiro Reily
AU - Vieira, Debora Braga
AU - Menck, Carlos Frederico Martins
N1 - Funding Information:
Financial support was provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (Process # 2014/15982-6 - FAPESP, São Paulo, Brazil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Process # 304270/2013-0 - CNPQ, Brasilia, Brazil) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brasilia, Brazil).
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Autophagy
KW - Chloroquine
KW - Glioma
KW - Glutathione
KW - Mitochondrial membrane potential
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84947998715&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2015.11.008
DO - 10.1016/j.freeradbiomed.2015.11.008
M3 - Article
C2 - 26577174
AN - SCOPUS:84947998715
SN - 0891-5849
VL - 90
SP - 91
EP - 100
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -