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In the present study, we investigated the mechanisms of the resistance to CD95-mediated cell death and the effects of interferon-cin modulating the susceptibility to CD95-induced apoptosis of human astroglioma cells. We found that interferon-cadministration sensitized cancer cells to CD95-med-iated apoptosis. | Interferon-c bolsters CD95 Fas-mediated apoptosis of astroglioma cells Anna M. Giammarioli1 Rosa Vona1 Lucrezia Gambardella1 Barbara Ascione1 Angela Maselli1 Cristiana Barbati2 Antonella Tinari3 and Walter Malorni1 1 Department of Therapeutic Research and Medicines Evaluation Istituto Superiore di Sanita Rome Italy 2 Department of CellBiology and Neurosciences Istituto Superiore di Sanita Rome Italy 3 Department of Technology and Health Istituto Superiore di Sanita Rome Italy Keywords apoptosis astrocytoma CD95 Fas interferon-y proteasome Correspondence A. M. Giammarioli Department of Therapeutic Research and Medicines Evaluation Section of Cell Aging and Degeneration Istituto Superiore di Sanita viale Regina Elena 299 00161 Rome Italy Fax 39 06 49903691 Tel 39 06 49902443 E-mail anna.giammarioli@iss.it Received 31 March 2009 revised 21 July 2009 accepted 11 August 2009 doi 10.1111 j.1742-4658.2009.07271.x In the present study we investigated the mechanisms of the resistance to CD95-mediated cell death and the effects of interferon-y in modulating the susceptibility to CD95-induced apoptosis of human astroglioma cells. We found that interferon-c administration sensitized cancer cells to CD95-med-iated 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 pro-teasome activity in the mechanism of sensitization by interferon-c was also detected probably as a result of the differing expression of catalytic protea-some subunits. Taken together these findings suggest that interferon-y could represent a promising candidate for modulating astroglioma cell apoptotic susceptibility. Introduction Astroglioma represents the most common primary brain tumor in humans. The prognosis of .
