Abstract
Background: The T-cell lymphoma cell line HuT78B1, selected for resistance to Fas-mediated apoptosis, resulted unexpectedly resistant to the apoptotic and cytotoxic effects of gemcitabine (dFdC). We investigated whether this resistance was due to the impairment of the Fas/Fas-ligand (FasL) system. Materials and Methods: dFdC effects were studied in HuT78B1 and in the parental Fas-sensitive HuT78 cells exposed to inhibitors of the Fas/FasL system. Results: FasL- and Fas-blocking antibodies did not interfere with dFdC-induced apoptosis in HuT78 cells, whereas inhibitors of caspase-8, -9, -1 or -3 had partial inhibitory effects. Notably, in HuT78B1 cells there was a markedly reduced dFdC accumulation notwithstanding a high activity of the activating enzyme deoxycytidine kinase. dFdC accumulation in HuT78 cells was unaffected by a Fas-blocking antibody. Conclusion: This is the first time that the selection of a Fas-resistant cell line led to the isolation of a cell clone unable to accumulate the deoxycytidine analog dFdC. Our results show that this alteration is independent from the impairment of the Fas/FasL system.
Lingua originale | English |
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pagine (da-a) | 851-857 |
Numero di pagine | 7 |
Rivista | Anticancer Research |
Volume | 24 |
Stato di pubblicazione | Published - 2004 |
All Science Journal Classification (ASJC) codes
- ???subjectarea.asjc.2700.2730???
- ???subjectarea.asjc.1300.1306???