Vitamin A treatment induces apoptosis through an oxidant-dependent activation of the mitochondrial pathway.
Even though retinoids are widely used as adjuvant in chemotherapeutic interventions to improve cancer cell death, their mechanism(s) of action involves multiple overlapping pathways that remain unclear. We have previously shown that vitamin A, the natural precursor of the retinoids, induces oxidative-dependent cytochrome c release from isolated mitochondria, suggesting a putative mechanism for apoptosis activation. Using Sertoli cells in culture, we show that retinol causes mitochondrial-dependent apoptosis, involving oxidative stress. Apoptosis was evaluated by nuclear morphology, DNA fragmentation, and caspase-3/7 activity. Retinol induced oxidant- and time-dependent imbalance of several mitochondrial parameters, cytochrome c release and caspase-3/7 activation, leading cells to commit apoptosis. All parameters tested were attenuated or blocked by trolox co-administration, suggesting that retinol induces apoptosis through oxidative damage, which mitochondria plays a pivotal role.
Klamt
Fábio
F
Center of Oxidative Stress Research, Department of Biochemistry, ICBS/Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. 00025267@ufrgs.br
Dal-Pizzol
Felipe
F
Gelain
Daniel Pens
DP
Dalmolin
Rodrigo Siqueira
RS
Birnfeld de Oliveira
Ramatis
R
Bastiani
Michele
M
Horn
Fabiana
F
Fonseca Moreira
José Cláudio
JC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D012708:Sertoli Cells / Q000648:ultrastructure; D014801:Vitamin A / Q000494:pharmacology*
D014801:Vitamin A; D045304:Cytochromes c; D053148:Caspase 3; D053179:Caspase 7