title: Enhancement of Selectivity of an Organometallic Anticancer Agent by Redox Modulation.
abstract: Combination with redox modulators can potentiate the anticancer activity and maximize the selectivity of organometallic complexes with redox-based mechanisms of action. We show that nontoxic doses of l-buthionine sulfoximine increase the selectivity of organo-Os complex FY26 for human ovarian cancer cells versus normal lung fibroblasts to 63-fold. This increase is not due to changes in the mechanism of action of FY26 but to the decreased response of cancer cells to oxidative stress.
authors.affiliation: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U.K.
authors.forename: Isolda
authors.initials: I
authors.lastname: Romero-Canelón
authors.affiliation: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U.K.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mos
authors.affiliation: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U.K.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology; D009992:Osmium / Q000737:chemistry / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; C000607188:FY26 osmium complex; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D013481:Superoxides; D009992:Osmium; D019328:Buthionine Sulfoximine; D005978:Glutathione