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Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death.

Abstract
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.
AuthorsEva Galeano, Elena Nieto, Ana Isabel García-Pérez, M Dolores Delgado, Montserrat Pinilla, Pilar Sancho
JournalLeukemia research (Leuk Res) Vol. 29 Issue 10 Pg. 1201-11 (Oct 2005) ISSN: 0145-2126 [Print] England
PMID15893819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Infective Agents, Local
  • Superoxides
  • Adenosine Triphosphate
  • Dequalinium
  • Oxygen
Topics
  • Adenosine Triphosphate (metabolism)
  • Anti-Infective Agents, Local (pharmacology)
  • Apoptosis (drug effects)
  • Cell Proliferation (drug effects)
  • Dequalinium (pharmacology)
  • Humans
  • K562 Cells
  • Leukemia, Promyelocytic, Acute (drug therapy)
  • Membrane Potentials (drug effects)
  • Mitochondria (drug effects, metabolism)
  • Necrosis
  • Oxygen (metabolism)
  • Superoxides (metabolism)
  • Tumor Cells, Cultured

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