Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Jan;91(1):41-51.
doi: 10.1111/j.1349-7006.2000.tb00858.x.

Adenovirus-mediated gene transduction of IkappaB or IkappaB plus Bax gene drastically enhances tumor necrosis factor (TNF)-induced apoptosis in human gliomas

N Shinoura  1 , N Yamamoto, Y Yoshida, T Fujita, N Saito, A Asai, T Kirino, H Hamada
Affiliations

Adenovirus-mediated gene transduction of IkappaB or IkappaB plus Bax gene drastically enhances tumor necrosis factor (TNF)-induced apoptosis in human gliomas

N Shinoura et al. Jpn J Cancer Res. 2000 Jan.

Abstract

Tumor necrosis factor-alpha (TNF), which was initially supposed to be a promising cancer therapeutic reagent, does not kill most types of cancer cells partly due to the activation of an anti-apoptotic gene, NF-kappaB. NF-kappaB forms an inactive complex with the inhibitor kappa B alpha (IkappaBalpha), which is rapidly phosphorylated and degraded in response to various extracellular signals. To disrupt this protective mechanism, we introduced an inhibitor kappa B alpha (IkappaBdN) gene, a deletion mutant gene lacking the nucleotides for the N-terminal 36 amino acids of IkappaBalpha, into human glioma cells (U251, T-98G, and U-373MG) via an adenoviral (Adv) vector in addition to treatment of the glioma cells with recombinant TNF. Immunohistochemical analysis revealed that NF-kappaB was translocated to nuclei by TNF treatment in U251 and T-98G cells, but not in U-373MG cells. Neither transduction of IkappaBdN nor treatment with TNF protein alone induced apoptosis in U251 and T-98G cells, whereas both cell lines underwent drastic TNF-induced apoptosis after transduction of IkappaBdN. On the other hand, U-373MG cells were refractory to TNF-induced apoptosis even when they were transduced with the IkappaBdN gene. U-373MG cells underwent drastically increased apoptosis when co-transduced with the IkappaBdN and Bax gene in the presence of TNF. Adv-mediated transfer of IkappaBdN or IkappaBdN plus Bax may be a promising therapeutic approach to treat gliomas through TNF-mediated apoptosis.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. ) Fukumura , D. , Salehi , H. A. , Witwer , B. , Tuma , R. F. , Melder , R. J. and Jain , R. K.Tumor necrosis factor alphainduced leukocyte adhesion in normal and tumor vessels: effect of tumor type, transplantation site, and host strain . Cancer Res. , 55 , 4824 – 4829 ( 1995. ). - PubMed
    1. ) Wright , J. L. and Merchant , R. E.Effects of an intratumoral injection of human recombinant tumor necrosis factor‐alpha on cerebrovascular permeability and leukocytic infiltration in a rat glioma model . Acta Neuropathol. (Berl.) , 93 , 78 – 86 ( 1997. ). - PubMed
    1. ) Tada , M. , Sawamura , Y. , Sakuma , S. , Suzuki , K. , Ohta , H. , Aida , T. and Abe , H.Cellular and cytokine responses of the human central nervous system to intracranial administration of tumor necrosis factor alpha for the treatment of malignant gliomas . Cancer Immunol. Immunother. , 36 , 251 – 259 ( 1993. ). - PMC - PubMed
    1. ) Del Maestro , R. F. , Lopez‐Torres , M. , Mcdonald , W. B. , Stroude , E. C. and Vaithilingam , I. S.The effect of tumor necrosis factor‐alpha on human malignant glial cells . J. Neurosurg. , 76 , 652 – 659 ( 1992. ). - PubMed
    1. ) Sakuma , S. , Sawamura , Y. , Tada , M. , Aida , T. , Abe , H. , Suzuki , K. and Taniguchi , N.Responses of human glioblastoma cells to human natural tumor necrosis factoralpha: susceptibility, mechanism of resistance and cytokine production studies . J. Neurooncol. , 15 , 197 – 208 ( 1993. ). - PubMed

Publication types

MeSH terms

LinkOut - more resources