Dequalinium induces human leukemia cell death by affecting the redox balance

Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways

“…2. According to our previous results [17][18][19], DQA induces both early (annexin V-FITC(+)/PI(−)) and late (annexin V-FITC(+)/PI(+)) apoptosis in NB4 cells ( Fig. 2A).…”

“…Antileukemic properties of DQA against the human leukemia cell lines, NB4 derived from acute promyelocytic leukemia, and K562, derived from chronic myeloid leukemia, are being studied in our group. We have reported the ability of DQA as a selective and potential antileukemic agent by interfering mitochondrial function, decreasing ATP and inducing oxidative stress which results in apoptosis by the intrinsic mitochondrial pathway [17][18][19][20]. Our previous results also support a cytotoxic effect of DQA on peripheral blood mononuclear cells from B-CLL patients that was higher than those from healthy donors [16].…”

“…Our previous studies demonstrate that DQA alters redox balance and causes oxidative stress in NB4 cells by decreasing GSH levels [19]. As can be seen in Figs.…”

“…1A). NB4 cells were treated with a low 2 M DQA concentration for 48 h or a high 20 M DQA concentration for 16 h. Both treatments have been previously shown to cause mitochondrial dysfunction, oxidative stress and apoptosis and/or necrosis on NB4 cells [17][18][19]. As it is shown in Fig.…”

“…Some components of MAPKs and PI3K/Akt pathways are redox-sensitive being modulated by the glutathione (GSH) content [2,28]. Our previous studies show that DQA affects redox balance and causes oxidative stress in NB4 cells by decreasing GSH levels [19]. The focus of this study centers in the DQA modulation of Raf/MEK/ERK1/2 and PI3K/Akt pathways in the NB4 cells as a possible mechanism of DQA-induced cell death.…”