Direct cytotoxicity produced by adenoviral-mediated interferon α gene transfer in interferon-resistant cancer cells involves ER stress and caspase 4 activation
作者： Z Yang , X-Q Zhang , C N P Dinney , W F Benedict
DOI: 10.1038/CGT.2011.26
关键词: Caspase 、 Biology 、 NLRP1 、 Caspase 4 、 Caspase 8 、 Alpha interferon 、 Cancer cell 、 Molecular biology 、 Caspase 10 、 Caspase 3
摘要: Over the past several years we have obtained considerable evidence indicating that adenoviruses-expressing interferon α (Ad-IFNα) can overcome resistance to IFNα protein itself. Since cancer cells infected with Ad-IFNα also show high perinuclear cytoplasmic expression, were interested in whether endoplasmic reticulum (ER) stress and cleavage of caspase 4 could a major role Ad-IFNα-produced cell death. Indeed, procaspase was upregulated cleaved as early 12 h after infection cells, which co-localized staining ER tracker. In contrast, immortalized normal human urothelial although exhibiting similar staining, showed no 4. Caspase not blocked by 8 specific inhibitor zIETD, activation independent activation. Blocking inhibited 3 containing cells. Finally, form (p10) detected Ad-IFNα-positive from urine patient following intravesical Ad-IFNα/Syn3 treatment. Therefore, appears be an important mechanism involved direct death produced occurs clinical setting.
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