NF-kB inhibition restores sensitivity to Fas-mediated apoptosis in lymphoma cell lines

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15 Citations (Scopus)

Abstract

Failure to perform the Fas-related apoptosis pathway can account for tumor resistance both to chemotherapeutic agents and to immunological effectors. We studied the role of NK-kappaB in Fas-resistance, employing the Fas-sensitive human T-lymphoma HuT78 cell line and its Fas-resistant variants HuT78B1 and HuT78G9. All these cell lines expressed high levels of constitutively activated NF-kappaB. Pretreatment of cells with NF-kappaB inhibitors (PDTC, MG132, or SN50) strongly enhanced CH11-induced apoptosis in HuT78 and Hut78G9 cells, while only MG132 showed a similar potentiating effect in HuT78B1. The described synergism was significantly inhibited by pretreatment with the anti-Fas-blocking antibody ZB4 or with the pancapsase inhibitor Z-VAD-FMK, but not by capsase-8 or -9 inhibitors. Overall, these data suggest that NF-kappaB inhibition may restore the Fas-pathway in Fas-resistant NF-kappaB-overexpressing tumors.
Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume1010
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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