Vitamin A treatment induces apoptosis through an oxidant-dependent activation of the mitochondrial pathway

Authors


Corresponding author at: Department de Bioquímica, ICBS/UFRGS, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS 90035-003, Brazil. Tel.: +55 51 3308 5577; fax: +55 51 3308 5535. 00025267@ufrgs.br

Abstract

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.

Ancillary