BID is a critical factor controlling cell viability regulated by IFN-?.

ABSTRACT: Clinical applications of human interferon (IFN)-? have met with varying degrees of success. Nevertheless, key molecules in cell viability regulated by IFN-? have not been clearly identified. Our previous study indicated that IFN (?, ?, and ?) receptor (IFNAR) 1/2- and IFN regulatory factor 9-RNA interference (RNAi) completely restored cell viability after IFN-? treatment in human ovarian adenocarcinoma OVCAR3 cells sensitive to IFN-?. In this study, IFNAR1/2- and IFN regulatory factor 9-RNAi inhibited the gene expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), but not of Fas ligand, after IFN-? treatment. In fact, TRAIL but not Fas ligand inhibited the viability of OVCAR3 cells. IFN-? notably upregulated the levels of TRAIL protein in the supernatant and on the membrane of OVCAR3 cells. After TRAIL signaling, caspase 8 inhibitor and BH3 interacting domain death agonist (BID)-RNAi significantly restored cell viability in response to IFN-? and TRAIL in OVCAR3 cells. Furthermore, BID-RNAi prevented both IFN-? and TRAIL from collapsing the mitochondrial membrane potential (??m). Finally, we provided important evidence that BID overexpression led to significant inhibition of cell viability after IFN-? or TRAIL treatments in human lung carcinoma A549 cells resistant to IFN-?. Thus, this study suggests that BID is crucial for cell viability regulated by IFN-? which can induce mitochondria-mediated apoptosis, indicating a notable potential to be a targeted therapy for IFN-? resistant tumors.

SUBMITTER: Tsuno T 

PROVIDER: S-EPMC3241910 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature