title: Anticancer activity of metal complexes: involvement of redox processes.
abstract: Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of "activation by reduction" as well as the "hard and soft acids and bases" theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology.
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria.
authors.forename: Ute
authors.initials: U
authors.lastname: Jungwirth
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kowol
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D056831:Coordination Complexes; D008024:Ligands; D013879:Thioredoxins; D005978:Glutathione