Interferon-gamma treatment elevates caspase-8 expression and sensitizes human breast tumor cells to a death receptor-induced mitochondria-operated apoptotic program

In this report, we have assessed the role of IFN-gamma as a sensitizing age nt in apoptosis mediated by activation of death receptor CD95 in breast tum or cells. Treatment of the tumor cell lines MCF-7 and MDA-MB231 with IFN-ga mma significantly facilitated apoptosis induced by CD95 receptor ligation a t the plasma membrane, independently of p53 status. Tn contrast, IFN-gamma treatment did nut enhance the apoptotic effect of the DNA-damaging drug, do xorubicin, Analysis of apoptosis regulators indicated that caspase-8 mRNA a nd protein levels were up-regulated in both of the cell lines after treatme nt with IFN-gamma, Furthermore, IFN-gamma sensitized MCF-7 and MDA-MR231 ce lls to CD95-mediated activation of caspase-8, induction of cytochrome c rel ease from mitochondria, and processing of caspase-9, Release of cytochrome c, caspases activation, and apoptosis were prevented in MCF-7 cells overexp ressing Bcl-2, Altogether these results indicate that IFN-gamma, maybe thro ugh the elevation of caspase-8 levels, sensitizes human breast tumor cells to a death receptor-mediated, mitochondria-operated pathway of apoptosis.