Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes.

ABSTRACT: Drugs capable of trapping topoisomerase II (Top2), an essential enzyme that cleaves DNA to remove naturally occurring knots and tangles, can serve as potent anticancer agents. The monofunctional platinum agent phenanthriplatin, cis-[Pt(NH₃)₂(phenanthridine)Cl](NO₃), is shown here to trap Top2 in addition to its known modes of inhibition of DNA and RNA polymerases. Its potency therefore combines diverse modes of action by which phenanthriplatin kills cancer cells. The observation that phenanthriplatin can act as a Top2 poison highlights opportunities to design nonclassical platinum anticancer agents with this novel mechanism of action. Such complexes have the potential to overcome current limitations with chemotherapy, such as resistance, and to provide trea

SUBMITTER: Riddell IA 

PROVIDER: S-EPMC5248983 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature