title: Iminophosphorane-organogold(III) complexes induce cell death through mitochondrial ROS production.
abstract: Gold compounds are being investigated as potential antitumor drugs. Some gold(III) derivatives have been shown to induce cell death in solid tumors but their mechanism of action differs from that of cisplatin, since most of these compounds do not bind to DNA. We have explored cellular events triggered by three different iminophosphorane-organogold(III) compounds in leukemia cells (a neutral compound with two chloride ligands [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}Cl(2)] 1, and two cationic compounds with either a dithiocarbamate ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-Me(2))]PF(6)2, or a water-soluble phosphine and a chloride ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(P{Cp(m-C(6)H(4)-SO(3)Na)(2)}(3)) Cl]PF(6)3). All three compounds showed higher toxicity against leukemia cells when compared to normal T-lymphocytes. Compounds 1 and 2 induced both necrosis and apoptosis, while 3 was mainly apoptotic. Necrotic cell death induced by 1 and 2 was Bax/Bak- and caspase-independent, while apoptosis induced by 3 was Bax/Bak-dependent. Reactive oxygen species (ROS) production at the mitochondrial level was a critical step in the antitumor effect of these compounds.
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, C/Pedro Cerbuna 12, Zaragoza, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vela
authors.forename: María
authors.initials: M
authors.lastname: Contel
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Gemma
authors.initials: G
authors.lastname: Azaceta
authors.forename: Isabel
authors.initials: I
authors.lastname: Marzo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010753:Phosphoranes / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds; D010753:Phosphoranes; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein