Adenovirus-mediated transfer of caspase-8 in combination with superrepressor of NF-kappaB drastically induced apoptosis in gliomas.
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.
Shinoura
N
N
Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan.
Yamamoto
N
N
Yoshida
Y
Y
Asai
A
A
Kirino
T
T
Hamada
H
H
D000256:Adenoviridae / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005354:Fibrosarcoma / Q000378:metabolism; D018014:Gene Transfer Techniques; D005910:Glioma / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D020672:I-kappa B Proteins; D015151:Immunoblotting; D000072000:NF-KappaB Inhibitor alpha; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases