Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L).
Biochem Pharmacol
; 57(10): 1199-208, 1999 May 15.
Article
en En
| MEDLINE
| ID: mdl-11230808
In order to investigate the molecular mechanism of the antineoplastic effects exerted by the antidepressive agents imipramine, clomipramine, and citalopram, we examined the effects of these compounds on cell viability, generation of reactive oxygen species (ROS), and mitochondrial membrane potential (DeltaPsi(m)) in human acute myeloid leukemia HL-60 cells. Our results indicate that exposure to these compounds causes a loss in cell viability by activating the apoptotic process, as identified by electron microscopy, DNA gel electrophoresis, and flow cytometry. The increased generation of ROS induced by these drugs was a relatively early event and preceded the loss of DeltaPsi(m). Overexpression of the antiapoptotic protein Bcl-2 or Bcl-X(L) prevents antidepressant-induced apoptosis, as well as loss of DeltaPsi(m), but does not affect the generation of ROS.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Especies Reactivas de Oxígeno
/
Apoptosis
/
Proteínas Proto-Oncogénicas c-bcl-2
/
Mitocondrias
/
Antidepresivos
Límite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
1999
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Reino Unido