Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities

Nicola Micale; Tanja Schirmeister; Roberta Ettari; Maria A Cinellu; Laura Maiore; Maria Serratrice; Chiara Gabbiani; Lara Massai; Luigi Messori

doi:10.1016/j.jinorgbio.2014.08.001

Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities

J Inorg Biochem. 2014 Dec:141:79-82. doi: 10.1016/j.jinorgbio.2014.08.001. Epub 2014 Aug 11.

Authors

Nicola Micale¹, Tanja Schirmeister², Roberta Ettari³, Maria A Cinellu⁴, Laura Maiore⁵, Maria Serratrice⁴, Chiara Gabbiani⁶, Lara Massai⁷, Luigi Messori⁸

Affiliations

¹ Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: nmicale@unime.it.
² Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, D-55099 Mainz, Germany.
³ Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli 25, 20122 Milan, Italy.
⁴ Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
⁵ Department of Chemical and Geological Sciences, University of Cagliari, S.S. 554, 09042 Monserrato, CA, Italy.
⁶ Department of Chemistry and Industrial Chemistry, via Risorgimento 35, 56126 Pisa, Italy.
⁷ Laboratory of "Metals in Medicine" (METMED), Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Firenze, Italy.
⁸ Laboratory of "Metals in Medicine" (METMED), Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Firenze, Italy. Electronic address: luigi.messori@unifi.it.

PMID: 25217719
DOI: 10.1016/j.jinorgbio.2014.08.001

Abstract

Six structurally diverse cytotoxic gold compounds are reported to cause profound and differential inhibition of the three main catalytic activities of purified 20S proteasome whilst auranofin, an established gold(I) drug in clinical use, is nearly ineffective. In particular, the gold(I) complex [(pbiH)Au(PPh3)]PF6, turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC50 values. The present results further support the view that proteasome inhibition may play a major--yet not exclusive--role in the cytotoxic actions of gold based anticancer agents.

Keywords: Anticancer drugs; Enzyme inhibition; Gold compounds; Proteasome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Auranofin / chemistry
Biocatalysis
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry*
Cytotoxins / chemical synthesis
Cytotoxins / chemistry*
Humans
Inhibitory Concentration 50
Organogold Compounds / chemical synthesis
Organogold Compounds / chemistry*
Proteasome Endopeptidase Complex / metabolism*
Proteasome Inhibitors / chemical synthesis
Proteasome Inhibitors / chemistry*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Coordination Complexes
Cytotoxins
Organogold Compounds
Proteasome Inhibitors
Auranofin
Proteasome Endopeptidase Complex