Dequalinium induces cell death in human leukemia cells by early mitochondrial alterations which enhance ROS production.
Dequalinium (DQA) has been proposed as a selective antitumoral agent due to its preferential accumulation in mitochondria of cancer cells. Our aim was a better understanding of DQA cytotoxicity. DQA-induced NB4 and K562 cell alterations are initiated within the first 30 min of treatment at a high DQA concentration with a mitochondrial membrane depolarization. Cytochrome c release to cytoplasm, superoxide anion overproduction and ATP depletion in NB4 cells induce, 16 h later, apoptosis by a typical caspase-9/caspase-3-dependent intrinsic pathway. K562 cells were more resistant to the DQA effect than NB4 cells, remaining viable for longer time periods.
Sancho
Pilar
P
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Galeano
Eva
E
Nieto
Elena
E
Delgado
M Dolores
MD
García-Pérez
Ana Isabel
AI
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003868:Dequalinium / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; D000255:Adenosine Triphosphate; D003868:Dequalinium; D053148:Caspase 3; D053453:Caspase 9; D010100:Oxygen