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.
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