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.
|Data di pubblicazione:||2004|
|Titolo:||Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated apoptosis|
|Autori:||MELI M; TOLOMEO M; D'ALESSANDRO N; GRIMAUDO S; NOTARBARTOLO M; PAPOFF G; RUBERTI G; RAUSA L; DUSONCHET L|
|Tipologia:||Articolo su rivista|
|Citazione:||MELI M, TOLOMEO M, D'ALESSANDRO N, GRIMAUDO S, NOTARBARTOLO M, PAPOFF G, et al. (2004). Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated apoptosis. ANTICANCER RESEARCH, 24, 851-857.|
|Appare nelle tipologie:||01 - Articolo su rivista|