Interferon-gamma bolsters CD95/Fas-mediated apoptosis of astroglioma cells.
In the present study, we investigated the mechanisms of the resistance to CD95-mediated cell death and the effects of interferon-gamma in modulating the susceptibility to CD95-induced apoptosis of human astroglioma cells. We found that interferon-gamma administration sensitized cancer cells to CD95-mediated apoptosis. The mechanism underlying this sensitization appeared to be associated with a framework of cell changes, including up-regulation of death receptor at the cell surface, pro-apoptotic molecule Bax and Bak over-expression and mitochondria hyperpolarization, as is known to be associated with cell sensitization to apoptosis. An involvement of the proteasome activity in the mechanism of sensitization by interferon-gamma was also detected, probably as a result of the differing expression of catalytic proteasome subunits. Taken together, these findings suggest that interferon-gamma could represent a promising candidate for modulating astroglioma cell apoptotic susceptibility.
Giammarioli
Anna M
AM
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanita', Rome, Italy. anna.giammarioli@iss.it
Vona
Rosa
R
Gambardella
Lucrezia
L
Ascione
Barbara
B
Maselli
Angela
A
Barbati
Cristiana
C
Tinari
Antonella
A
Malorni
Walter
W
D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism*; D015153:Blotting, Western; D053455:Caspase 10 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000648:ultrastructure; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D000998:Antiviral Agents; D019014:fas Receptor; D007371:Interferon-gamma; C505530:CASP8 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D046988:Proteasome Endopeptidase Complex