Implication of mitochondria-derived ROS and cardiolipin peroxidation in N-(4-hydroxyphenyl)retinamide-induced apoptosis.
We have studied the effect of N-(4-hydroxyphenyl)retinamide on either malignant human leukaemia cells or normal cells and investigated its mechanism of action. We demonstrate that 4HPR induces reactive oxygen species increase on mitochondria at a target between mitochondrial respiratory chain complex I and II. Such oxidative stress causes cardiolipin peroxidation which in turn allows cytochrome c release to cytosol, caspase-3 activation and therefore apoptotic consumption. Moreover, this apoptotic pathway seems to be bcl-2/bax independent and count only on malignant cells but not normal nor activated lymphocytes.
Asumendi
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Department of Cell Biology and Histology, School of Medicine and Dentistry, University of The Basque Country, Leioa- 48940, Bizkaia, Spain. gcpasmaa@lg.ehu.es
Morales
M C
MC
Alvarez
A
A
Aréchaga
J
J
Pérez-Yarza
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002308:Cardiolipins / Q000378:metabolism*; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002308:Cardiolipins; D017382:Reactive Oxygen Species; D017313:Fenretinide