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NF-  B Inhibition Restores Sensitivity to Fas-Mediated Apoptosis in Lymphoma Cell Lines
aDepartment of Pharmacological Sciences, Università di Palermo, 90127 Palermo, Italy bDepartment of Haematology and AIDS Center, Università di Palermo, 90127 Palermo, Italy
Address for correspondence; Dr. Maria Meli, Department of Pharmacological Sciences, University of Palermo, via del Vespro 129, 90127 Palermo, Italy. Voice: +39 091 6553261; fax: +39 091 6553249. mmeli{at}unipa.it Ann. N.Y. Acad. Sci. 1010: 232-236 (2003).
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-
 B 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-B. Pretreatment of cells with NF-B 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-B inhibition may restore the Fas-pathway in Fas-resistant NF-B-overexpressing tumors.
Key Words: apoptosis • NF- B • MG132 • Fas/FasL systemThis article has been cited by other articles:
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