Affiliations: Departamento de Biología Celular, Fisiología
e Inmunología, Universidad de Córdoba, Spain | Laboratorio Andaluz de Biología, Universidad
Pablo de Olavide, Sevilla, Spain
Note: [] Address for correspondence: Dr. J.M. Villalba, Departamento de
Biología Celular, Fisiología e Inmunología, Facultad de
Ciencias, Universidad de Córdoba, Campus Rabanales, Edificio Severo
Ochoa, 3a planta, 14014-Córdoba, Spain
Abstract: We have previously shown that inhibition of NAD(P)H:quinone acceptor
oxidoreductase 1 with dicoumarol decreases growth and viability of HL-60 cells
in the absence of serum. Here we demonstrate that culturing HL-60 cells in
serum-free medium in the presence of dicoumarol results in a significant
potentiation of apoptosis. However, when cells were preincubated for 24 h
without serum before they were treated with dicoumarol, the effect of the
inhibitor on cell growth and death was much lower. We have investigated
cellular changes induced in HL-60 cells by removal of serum that could account
for protection against the effects of dicoumarol. Serum removal induced
significant increases of NAD(P)H:quinone acceptor oxidoreductase 1,
particularly at 32 h after serum withdrawal. Total amounts of ubiquinone in
cells were unchanged but, its reduction state paralleled the observed increase
in quinone reductase activity. Levels of the antiapoptotic protein Bcl-2 were
also significantly increased after serum removal. Our results indicate that
removal of serum evokes an antioxidant protective response that make HL-60
cells less sensitive to cell death induced by inhibition of NAD(P)H:quinone
acceptor oxidoreductase 1 with dicoumarol.
Journal: BioFactors, vol. 18, no. 1-4, pp. 219-228, 2003
