Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death.
Dequalinium (DQA) is a delocalized lipophylic cation that selectively targets the mitochondria of carcinoma cells. However, the underlying mechanisms of DQA action are not yet well understood. We have studied the effects of DQA on two different leukemia cell lines: NB4, derived from acute promyelocytic leukemia, and K562, derived from chronic myeloid leukemia. We found that DQA displays differential cytotoxic activity in these cell lines. In NB4 cells, a low DQA concentration (2microM) induces a mixture of apoptosis and necrosis, whereas a high DQA concentration (20microM) induces mainly necrosis. However, K562 cell death was always by necrosis as the cells showed a resistance to apoptosis at all time-periods and DQA concentrations assayed. In both cell lines, the cell death seems to be mediated by alterations of mitochondrial function as evidenced by loss of mitochondrial transmembrane potential, O2*- accumulation and ATP depletion. The current study improves the knowledge on DQA as a novel anticancer agent with a potential application in human acute promyelocytic leukemia chemotherapy.
Galeano
Eva
E
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Nieto
Elena
E
García-Pérez
Ana Isabel
AI
Delgado
M Dolores
MD
Pinilla
Montserrat
M
Sancho
Pilar
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003868:Dequalinium / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000891:Anti-Infective Agents, Local; D013481:Superoxides; D000255:Adenosine Triphosphate; D003868:Dequalinium; D010100:Oxygen