Anticancer activity of metal complexes: involvement of redox processes

Ute Jungwirth, Christian R Kowol, Bernhard K Keppler, Christian G Hartinger, Walter Berger, Petra Heffeter

Research output: Contribution to journalReview article

271 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1085-127
Number of pages43
JournalAntioxidants & Redox Signaling
Volume15
Issue number4
DOIs
Publication statusPublished - 15 Aug 2011

Keywords

  • Animals
  • Anticarcinogenic Agents/chemistry
  • Coordination Complexes/chemistry
  • Glutathione/metabolism
  • Homeostasis/drug effects
  • Humans
  • Ligands
  • Oxidation-Reduction/drug effects
  • Oxidative Stress
  • Thioredoxins/metabolism

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  • Cite this

    Jungwirth, U., Kowol, C. R., Keppler, B. K., Hartinger, C. G., Berger, W., & Heffeter, P. (2011). Anticancer activity of metal complexes: involvement of redox processes. Antioxidants & Redox Signaling, 15(4), 1085-127. https://doi.org/10.1089/ars.2010.3663