TY - JOUR
T1 - In vitro modulation of CD95 expression on a human glioblastoma cell line by various chemotherapeutic drugs
AU - Ciusani, E.
AU - Perego, P.
AU - Salmaggi, A.
AU - Carenini, N.
AU - Eoli, M.
AU - Silvani, A.
AU - Boiardi, A.
AU - Zunino, F.
PY - 2000
Y1 - 2000
N2 - The CD95-mediated pathway may be relevant in regulating drug sensitivity of tumor cells because this system, consisting of a membrane-bound isoform and its natural ligand (CD95L), might be modulated in response to drug treatment. In this study, using a CD95+ human glioblastoma cell line, we investigated the in vitro effects of various chemotherapeutic drugs on CD95 expression. Alterations in the susceptibility of this cell line to Fas-dependent apoptosis following drug exposure were also evaluated. Our results show that in vitro treatment of GBM cell with mitoxantrone, topotecan and CPT-83 induced an up-regulation of CD95 expression, whereas other drugs such as cisplatin and taxol did not. In the case of topotecan and CPT-83, the drug-induced up-regulation of CD95 was concomitant to an increased susceptibility of GBM cells to Fas-dependent apoptosis. The observed up-regulation of CD95 expression and Fas-dependent apoptosis might have important therapeutic implications because cells could be sensitive to specific DNA-damaging agents through activation of the CD95 pathway. The profile of expression of CD95 might be a useful additional tool in the choice of the optimal chemotherapeutic regimen in glioblastoma.
AB - The CD95-mediated pathway may be relevant in regulating drug sensitivity of tumor cells because this system, consisting of a membrane-bound isoform and its natural ligand (CD95L), might be modulated in response to drug treatment. In this study, using a CD95+ human glioblastoma cell line, we investigated the in vitro effects of various chemotherapeutic drugs on CD95 expression. Alterations in the susceptibility of this cell line to Fas-dependent apoptosis following drug exposure were also evaluated. Our results show that in vitro treatment of GBM cell with mitoxantrone, topotecan and CPT-83 induced an up-regulation of CD95 expression, whereas other drugs such as cisplatin and taxol did not. In the case of topotecan and CPT-83, the drug-induced up-regulation of CD95 was concomitant to an increased susceptibility of GBM cells to Fas-dependent apoptosis. The observed up-regulation of CD95 expression and Fas-dependent apoptosis might have important therapeutic implications because cells could be sensitive to specific DNA-damaging agents through activation of the CD95 pathway. The profile of expression of CD95 might be a useful additional tool in the choice of the optimal chemotherapeutic regimen in glioblastoma.
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M3 - Article
AN - SCOPUS:33845345632
VL - 21
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
IS - 4 SUPPL.
ER -