title: Innocent But Deadly: Nontoxic Organoiridium Catalysts Promote Selective Cancer Cell Death.
abstract: We demonstrate that nontoxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum antiproliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to lowering of the 50 % growth inhibition concentration (IC50) of the Pt drug carboplatin by up to ∼30-50 %. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes. Cell culture studies indicate that cancer cells that were administered with Ir show significantly higher reactive oxygen species concentrations as well as NAD+/NADH ratios (oxidized vs. reduced nicotinamide adenine dinucleotide) than Ir-treated non-cancer cells. These biochemical changes are consistent with a catalytic transfer hydrogenation cycle involving the formation of iridium-hydride species from the reaction of the iridium catalysts with NADH and subsequent oxidation in air to generate hydrogen peroxide.
authors.affiliation: Department of Chemistry, University of Houston, 4800 Calhoun Road, Houston, TX, 77004, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of Houston, 4800 Calhoun Road, Houston, TX, 77004, USA.
authors.forename: Sohini
authors.initials: S
authors.lastname: Bose
authors.affiliation: Department of Chemistry, University of Houston, 4800 Calhoun Road, Houston, TX, 77004, USA.
authors.forename: Anh H
authors.initials: AH
authors.lastname: Ngo
authors.affiliation: Department of Chemistry, University of Houston, 4800 Calhoun Road, Houston, TX, 77004, USA.
authors.forename: Loi H
authors.identifier: 0000-0002-8859-141X
authors.initials: LH
authors.lastname: Do
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D016190:Carboplatin / Q000633:toxicity; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D009243:NAD / Q000737:chemistry; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D009243:NAD; D007495:Iridium; D016190:Carboplatin
keywords: biocatalysis; cancer; chemosensitization; drug discovery; iridium catalysis