Activity, Neurotoxicity and Photon Activation Therapy Effect in Human Tumour Cells of Heavy Metal-Based Complexes

Cisplatin (CDDP) is an anticancer drug widely used in clinic for the treatment of several solid tumours, despite its high effectiveness treatment is still limited by severe side effects and by inherited or acquired resistance phenomena. These drawbacks have stimulated the search of alternative strategies based on different metals offering a better toxicity profile while maintaining the same level of efficacy as platinum-based treatments. Recently we evaluated the cytotoxicity and neurotoxicity of our newly developed promising water soluble anticancer complexes ([Cu(PTA)4]PF6, [Cu(thp)4]PF6, [Au(PTA)4]PF6, [Au(thp)4]PF6) on A549 non-small cell lung cancer (NSCLC) and IGROV-1 ovarian human cancer cells, CDDP being used as drug reference. In our model CDDP resulted neurotoxic at concentrations achievable in plasma of patients treated with the same drugs. Similarly the gold-based compound [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 calculated for the tested cancer cell lines. On the contrary, both copper-based compounds and [Au(thp)4]PF6 were neurotoxic at higher concentrations with respect to the IC50 obtained in tumour cell lines tested. We then tested at the ID17 beamline of the ESRF the efficacy of synchrotron radiation (SR) to trigger the Auger effect in A549 and IGROV-1 cells containing a high Z-number element. Irradiation of cells pre-treated with CDDP or [Cu(PTA)4]PF6 concentrations allowing roughly 90% of cell survival induced an enhancement in cellular death with respect to drug and irradiation alone. With the other compounds no cell death enhancement was observed. 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, considering the anticancer activity and the neurotoxic profile of [Cu(PTA)4]PF6, our data suggest that copper-based drugs represent new and promising compounds in anticancer treatment also in combination with SR.