Anhydroretinol induces oxidative stress and cell death

The retro-retinoid anhydroretinol (AR), a physiological metabolite of retinol (vitamin A), induces cell death in multiple in vitro systems. AR-induced cell death is blocked by retinol and its metabolite 14-hydroxy-4,14-retro-retinol. AR has been shown also to prevent mammary cancer induced by N-meth...

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Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 59; no. 16; pp. 3985 - 3990
Main Authors YANQIU CHEN, BUCK, J, DERGUINI, F
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 15.08.1999
Subjects
Animals
Antineoplastic agents
Antioxidants - pharmacology
Biological and medical sciences
Cell Death - drug effects
Chemotherapy
Drug Antagonism
Humans
Jurkat Cells
Medical sciences
Oxidative Stress - drug effects
Pharmacology. Drug treatments
Rats
Reactive Oxygen Species - metabolism
Vitamin A - analogs & derivatives
Vitamin A - toxicity
Antineoplastic agent
Oxidative stress
Cell death
Metabolite
Established cell line
Cytotoxicity
Antioxidant
Mechanism of action
Lymphoblastoid cell
In vitro
Retinol
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Summary:The retro-retinoid anhydroretinol (AR), a physiological metabolite of retinol (vitamin A), induces cell death in multiple in vitro systems. AR-induced cell death is blocked by retinol and its metabolite 14-hydroxy-4,14-retro-retinol. AR has been shown also to prevent mammary cancer induced by N-methyl-N-nitrosourea in rats. We report that AR kills cells by generating reactive oxygen species. Direct measurements show that the addition of AR to lymphoblastoid cells increases the intracellular oxidative stress in a time- and dose-dependent manner. Furthermore, the amount of induced oxidative stress directly correlates with the number of dying cells. The addition of retinol, 14-hydroxy-4,14-retro-retinol, or the antioxidant, alpha-tocopherol (vitamin E), decreases AR-induced oxidative stress and proportionally reduces AR-induced cell death. In contrast, pretreatment with caspase inhibitors, known to inhibit apoptosis, has no effect on AR-induced cell death. This is the first demonstration of cellular reactive oxygen species production by a natural retinoid.
ISSN:0008-5472
1538-7445