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Biochemistry and Biophysics |
Treatment Elevates Caspase-8 Expression and Sensitizes Human Breast Tumor Cells to a Death Receptor-induced Mitochondria-operated Apoptotic Program1
Instituto de Parasitología y Biomedicina Consejo Superior de Investigaciones Centificas, 18001 Granada, Spain
In this report, we have assessed the role of IFN-
as a sensitizing
agent in apoptosis mediated by activation of death receptor CD95 in
breast tumor cells. Treatment of the tumor cell lines MCF-7 and
MDA-MB231 with IFN-
significantly facilitated apoptosis induced by
CD95 receptor ligation at the plasma membrane, independently of
p53 status. In contrast, IFN-
treatment did not enhance the
apoptotic effect of the DNA-damaging drug, doxorubicin. Analysis of
apoptosis regulators indicated that caspase-8 mRNA and protein levels
were up-regulated in both of the cell lines after treatment with
IFN-
. Furthermore, IFN-
sensitized MCF-7 and MDA-MB231 cells to
CD95-mediated activation of caspase-8, induction of cytochrome
c release from mitochondria, and processing of
caspase-9. Release of cytochrome c, caspases activation,
and apoptosis were prevented in MCF-7 cells overexpressing Bcl-2.
Altogether these results indicate that IFN-
, maybe through the
elevation of caspase-8 levels, sensitizes human breast tumor cells to a
death receptor-mediated, mitochondria-operated pathway of apoptosis.
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