Adenovirus-mediated transfer of caspase-8 in combination with superrepressor of NF-κB drastically induced apoptosis in gliomas

Inhibition of NF-kappa B in the presence of tumor necrosis factor-alpha (TNF) is supposed to be a promising cancer therapeutic approach, since it disrupts the protective mechanism of NF-kappa B activated by TNF. To test this approach in gliomas, we introduced a superrepressor of NF-kappa B, an N-terminal deleted form of inhibitor kappa B alpha (I kappa BdN) gene, to human glioma cells (U251 and U-373MG) via adenoviral vector (Adv) in the presence of TNF. U-373MG cells were refractory to TNF-induced apoptosis even when they were transduced with the I kappa BdN gene. On the other hand, transduction of I kappa BdN drastically augmented caspase-8-mediated apoptosis in U-373MG cells. Similar results were obtained in U251. cells. Cotransduction of I kappa BdN and caspase-8 induced cleavage of PARP. Taken together, Adv-mediated transfer of I kappa BdN plus caspase-8 may be a promising therapeutic approach to treat gliomas. (C) 2000 Academic Press.