Cell death enhancement after irradiation with monochromatic syncrotron X-rays platinum K-edge in cisplatin pre-treated human non small cell lung cancer, ovarian and stem glioma cells

Cisplatin is an antineoplastic drug widely used in clinic for the treatment of several solid tumours. However, at times, the side effects related to cisplatin-based anticancer therapy often outweigh the benefits. Several of these side effects are now manageable with effective treatment planning and supportive care strategies (e.g. anti-emetics, hematopoietics growth factors, physical treatments, hyperhydration), but others are still unsolved, can be dose-limiting and represent an unmet clinical need, for instance nervous system damage. Therefore, the identification of new anticancer strategies able to offer a better toxicity profile maintaining the same level of efficacy as platinum-based treatments would be highly desirable. We tested the efficacy of synchrotron radiation to trigger the Auger effect in the living human A549 non-small cell lung cancer (NSCLC) and IGROV-1 ovarian cancer cells pre-treated with cisplatin. Furthermore we tested the anticancer treatment in human VIPI glioblastoma stem cells that seem to be one of the most important determinants in the extraordinary resistance of GBL to any treatment tested so far. The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, where a high-fluence monochromatic beam adjustable from 20 to 80 keV is available. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Control cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. On cisplatin-treated cells at a concentrations inducing 80% of cell survival with respect to the control, no differences were observed in cell survival when cells were irradiated either above or below the K-shell edge of platinum, suggesting that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. At lower cisplatin concentrations, determining 95-90% of cell survival an enhancement in the cellular death was observed, with respect to conventional irradiation conditions was observed when cells were irradiated with beams either above or below the platinum K-shell edge. Our results suggest that SR-enhanced CDDP activity might allow the use of a reduced dose of CDDP thus achieving side effects minimization due to the exposure of normal cells/tissues to less toxic doses. Furthermore SR-enhanced CDDP activity might enhance CDDP effect on cancer stem cells obtained from human glioblastoma. Reliable in vivo animal models might be investigated in future experiments to assess activity and toxicity of the proposed treatment in cancer-bearing mice.