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The approved platinum drugs continue to have a major role in cancer treatment. However, despite their efficacy, serious side effects often prevent their administration at full efficacious doses or may considerably affect patients’ quality of  life. Hence, there is an urgent need to find safer and better-tolerated chemotherapeutic drugs. In this work we investigated in vitro the activity and the neurotoxicity of new anticancer complexes based on copper ([Cu(PTA)4]PF6; [Cu(thp)4]PF6), gold ([Au(PTA)4]PF6) and platinum ([PtCl2(cis-1,4-DACH)]; [Pt(1,1’-CBDCA)(cis-1,4-DACH)]). Cytotoxicity was tested by MTT assay in a panel of human cancer cells. Neurotoxicity was evaluated by an in vitro model based on organotypic cultures of DRG from E15 rat embryos. Since the ubiquitin-proteasome system is a cancer cell molecular target of copper and gold based-drugs, we evaluated, by fluorimetric assay, their ability to hinder the proteasome machinery in DRG neurons. At 48 hours, both copper compounds were not neurotoxic even at higher concentrations with respect to the IC50 calculated in cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50. [PtCl2(cis-1,4-DACH)] elicited a neurotoxicity slightly lower with respect to oxaliplatin. Conversely, [Pt(1,1’-CBDCA)(cis-1,4-DACH)] showed a reduced neurotoxicity compared with the reference drug. Both copper-based compounds, that are not neurotoxic, do not inhibit proteasome activity in DRG neurons. Contrarily, the neurotoxic complex [Au(PTA)4]PF6, induces a significant inhibition of proteasome activity. Our results, together with the low IC50 of the copper and platinum based complexes, suggest them as promising compounds providing support to further in vivo studies

journal of alzheimer's disease

Abstracts for the Second International Meeting of the Milan Center for Neuroscience (Neuromi): Prediction and Prevention of Dementia: New Hope (Milan, July 6–8, 2016)