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New Findings in the Signaling Pathways of cis and trans Platinum Iodido Complexes’ Interaction with DNA of Cancer Cells
journal contributionposted on 2019-12-03, 18:38 authored by Adoración G. Quiroga, Marta Cama, Natalia Pajuelo-Lozano, Amparo Álvarez-Valdés, Isabel Sanchez Perez
We have selected a series of aliphatic amine platinum compounds bearing chloride and/or iodide as the leaving groups. The complexes’ cytotoxicity and interaction with DNA indicated differences in the reactivity. Now, we are reporting on the analysis of their molecular mechanism of action on gastric cancer cells. Our data reveals differences between them. Chlorido drugs showed similar behavior to cisplatin; they both required p53 to induce apoptosis but only cis-ipa showed DNA damage requirement for apoptosis induction. On the contrary, cis and trans iodido induced cell death independent of p53 activity, and they induced cell death through Bid activation, so their toxicity could be enhanced in a combined treatment with novel Bcl-2 protein family inhibitors. We also report the structural features of the DNA adduct for one of the complexes by X-ray diffraction. These findings represent a step forward in the search for new platinum-derived agents more specific and effective in the treatment of cancer.