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Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Magherini, Francesca and Modesti, Alessandra and Bini, Luca and Puglia, Michele and Landini, Ida and Nobili, Stefania and Mini, Enrico and Cinellu, Maria Agostina and Gabbiani, Chiara and Messori, Luigi (2010) Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study. Journal of Biological Inorganic Chemistry, Vol. 15 (4), p. 573-582. eISSN 1432-1327. Article.

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DOI: 10.1007/s00775-010-0624-3

Abstract

We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

Item Type:Article
ID Code:4275
Status:Published
Refereed:Yes
Uncontrolled Keywords:Proteomic, gold compound
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01 Dipartimenti > Chimica
Publisher:Springer Berlin / Heildelberg
eISSN:1432-1327
Copyright Holders:© SBIC 2010
Deposited On:26 Jul 2010 15:56

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