Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs (Articolo in rivista)

Type
Label
  • Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.ccr.2009.02.026 (literal)
Alternative label
  • Bindoli A., Rigobello M.P., Scutari G., Gabbiani C., Casini A., Messori L. (2009)
    Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs
    in Coordination chemistry reviews (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bindoli A., Rigobello M.P., Scutari G., Gabbiani C., Casini A., Messori L. (literal)
Pagina inizio
  • 1692 (literal)
Pagina fine
  • 1707 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 253 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Neuroscienze (CNR), Sezione di Padova, c/o Dipartimento di Chimica Biologica, Viale G. Colombo 3, 35121 Padova, Italy Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy Laboratory of \"Metals in Medicine\" (METMED), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy Laboratory of Organometallic and Medicinal Chemistry, Ecole Polytechnique Fédérale de Lausanne, SB-ISIC LCOM, BCH 2404, CH-1015 Lausanne, Switzerland (literal)
Titolo
  • Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs (literal)
Abstract
  • The thioredoxin system plays a key role in regulating the overall intracellular redox balance. It basically comprises the small redox protein thioredoxin (Trx), nicotinamide adenine dinucleotide phosphate, in its reduced form (NADPH), and thioredoxin reductase (TrxR), a large homodimeric selenzoenzyme controlling the redox state of thioredoxin. Details of the thioredoxin system are provided herein, particular emphasis being given to the protein chemistry of thioredoxin reductases. Several lines of evidence point out today that the thioredoxin system represents an effective \"druggable\" target for the development of new anticancer agents. Accordingly, a number of established anticancer agents were retrospectively found to be potent inhibitors of thioredoxin reductases and to induce severe oxidative stress. During the last decade a variety of gold compounds, either gold(I) or gold(III), were reported to manifest outstanding antitumor properties, forming a promising class of experimental anticancer agents. In turn, recent studies have revealed that several cytotoxic gold compounds, either gold(I) or gold(III), are potent TrxR inhibitors. Details of their mechanism of selenoenzyme inhibition are currently under investigation, in our laboratory, and some newresultswill be anticipated here; notably, preferential gold targeting of active site selenolate could be experimentally supported. Based on the numerous experimental evidences now available, both at the molecular and cellular level,we propose that the relevant cytotoxic actions produced by gold compounds are mainly the result of potent inhibition of thioredoxin reductase; the alterations of mitochondrial functions, elicited by profound TrxR inhibition, would eventually lead to cell apoptosis. A general and unitary framework is thus offered to interpret the mode of action of cytotoxic gold compounds, according to which they should be primarily considered as antimitochondrial drugs. The peculiar properties of gold compounds highlighted in this review might be further exploited for the obtainment of newer and selective anticancer agents. (literal)
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