• Open Access

Sensitization of human glioblastomas to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by NF-κB inhibitors

Authors

  • Chinatsu Kasuga,

    1. Department of Neurosurgery, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Tomohiko Ebata,

    Corresponding author
    1. Department of Immunology, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
      To whom correspondence and reprint requests should be addressed. Tomohiko Ebata, Department of Immunology, Juntendo University School of Medicine. E-mail: tomohiko.ebata@nifty.com
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  • Nobuhiko Kayagaki,

    1. Department of Immunology, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Hideo Yagita,

    1. Department of Immunology, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Makoto Hishii,

    1. Department of Neurosurgery, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Hajime Aral,

    1. Department of Neurosurgery, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Kiyoshi Sato,

    1. Department of Neurosurgery, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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  • Ko Okumura

    1. Department of Immunology, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421
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To whom correspondence and reprint requests should be addressed. Tomohiko Ebata, Department of Immunology, Juntendo University School of Medicine. E-mail: tomohiko.ebata@nifty.com

Abstract

Glioblastoma is the most malignant form of primary brain tumor in adults, with no effective therapy and a low survival rate. TRAIL is a member of the TNF family, which selectively induces apoptosis in certain neoplastic cells, but not normal cells. In this study, we investigated the sensitivity of 7 human glioblastoma cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These glioblastoma cell lines expressed TRAIL-R2, but not TRAIL-R1, R3, or R4. However, no correlation was observed between the TRAIL sensitivity and the TRAIL-R2 expression level, suggesting that there is an additional determinant of TRAIL sensitivity. Treatments with NF-κB inhibitors, such as LLnL, MG132, and SN50, significantly increased the sensitivity of glioma cells to TRAIL. These results suggested that activation of NF-κB is a protective mechanism against TRAIL-induced cell death in some glioma cells, and thus NF-κB inhibitors may be useful to improve the clinical treatment of glioblastoma with TRAIL.

Abbreviations:
TNF

tumor necrosis factor

NF-κB

nuclear factor κB

1κB

inhibitory NF-κB

IKK

IκB kinase

FILP

FLICE inhibitory protein

IAP

inhibitor of apoptosis

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