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  • Title: Adenovirus-mediated transfer of caspase-8 in combination with superrepressor of NF-kappaB drastically induced apoptosis in gliomas.
    Author: Shinoura N, Yamamoto N, Yoshida Y, Asai A, Kirino T, Hamada H.
    Journal: Biochem Biophys Res Commun; 2000 May 10; 271(2):544-52. PubMed ID: 10799332.
    Abstract:
    Inhibition of NF-kappaB 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-kappaB activated by TNF. To test this approach in gliomas, we introduced a superrepressor of NF-kappaB, an N-terminal deleted form of inhibitor kappa B alpha (IkappaBdN) 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 IkappaBdN gene. On the other hand, transduction of IkappaBdN drastically augmented caspase-8-mediated apoptosis in U-373MG cells. Similar results were obtained in U251 cells. Cotransduction of IkappaBdN and caspase-8 induced cleavage of PARP. Taken together, Adv-mediated transfer of IkappaBdN plus caspase-8 may be a promising therapeutic approach to treat gliomas.
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