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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2008) 32, 100–106 (Printed in Great Britain)
Vitamin A treatment induces apoptosis through an oxidant-dependent activation of the mitochondrial pathway
Fábio Klamta*, Felipe Dal‑Pizzolb, Daniel Pens Gelaina, Rodrigo Siqueira Dalmolina, Ramatis Birnfeld de Oliveiraa, Michele Bastianic, Fabiana Hornc and José Cláudio Fonseca Moreiraa
aCenter of Oxidative Stress Research, Department of Biochemistry, ICBS/Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
bDepartment of Medicine, University of Extremo Sul Catarinense (UNESC), Criciúma, Brazil
cDepartment of Biophysics, IB/UFRGS, Porto Alegre, Brazil


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.


Key words: Retinol, Mitochondria, Apoptosis, Cytochrome c, Oxidative stress.

*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.


Received 16 March 2007/30 April 2007; accepted 27 August 2007

doi:10.1016/j.cellbi.2007.08.018


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)