Abstract 2499: Sulfasalazine sensitizes glioblastoma cells to radiation treatment

Abstract

Abstract Glioblastomas (GBMs) are lethal cancers with a limited response to ionizing radiation. Recent studies suggest that Sulfasalazine (SAS), a drug used to treat inflammatory bowel disease, inhibits the xCT antiporter system in glioma cells, thereby blocking their uptake of cystein. Since the availability of cystein is a rate limiting step in intracellular antioxidant production, we wanted to investigate whether sulfasalazine sensitizes glioma cells to radiation. SAS effect on glioma cell growth was investigated using an electric cell substrate impedance sensing (ECIS) instrument. All cell lines showed altered growth curves in response to SAS treatment. To assess the effect of blocking the xCT antiporter, intracellular levels of the antioxidant glutathione were measured. With increasing doses of SAS, glutathione levels decreased in a dose response manner. Further, U251 glioma cells were treated with escalating doses of SAS, alone or in combination with radiation (8 Gy). Nuclear integrity was evaluated to estimate cell death following treatment. In addition, cell death and viability were investigated using live/dead staining and MTS assay respectively. All treatment groups exhibited increased rates of cell death compared to untreated controls. However, a combination of SAS and radiation resulted in higher levels of cell death, than radiation or SAS administered alone. In order to assess whether this can be exploited therapeutically, we are currently preparing to treat nude rats harbouring gliblastoma biopsy xenografts with SAS, alone or in combination with radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2499. doi:10.1158/1538-7445.AM2011-2499