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 originaleEnglish
pagine (da-a)851-857
Numero di pagine7
RivistaAnticancer Research
Volume24
Stato di pubblicazionePublished - 2004

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cita questo

@article{78087ee797964d38b4b1e64263b96af9,
title = "Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated apoptosis",
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.",
author = "Natale D'Alessandro and Luisa Dusonchet and Luciano Rausa and Stefania Grimaudo and Maria Meli and {Notarbartolo Di Villarosa}, Monica and Giuliana Papoff and Giovina Ruberti",
year = "2004",
language = "English",
volume = "24",
pages = "851--857",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",

}

TY - JOUR

T1 - Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated apoptosis

AU - D'Alessandro, Natale

AU - Dusonchet, Luisa

AU - Rausa, Luciano

AU - Grimaudo, Stefania

AU - Meli, Maria

AU - Notarbartolo Di Villarosa, Monica

AU - Papoff, Giuliana

AU - Ruberti, Giovina

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/14028

M3 - Article

VL - 24

SP - 851

EP - 857

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

ER -