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Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds

Guidi, Francesca and Landini, Ida and Puglia, Michele and Magherini, Francesca and Gabbiani, Chiara and Cinellu, Maria Agostina and Nobili, Stefania and Fiaschi, Tania and Bini, Luca and Mini, Enrico and Messori, Luigi and Modesti, Alessandra (2012) Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds. Metallomics, Vol. 4 (3), p. 307-314. eISSN 1756-591X. Article.

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DOI: 10.1039/C2MT00083K

Abstract

Platinum-based chemotherapy is the primary treatment for human ovarian cancer. Overcoming platinum resistance has become a critical issue in the current chemotherapeutic strategies of ovarian cancer as drug resistance is the main reason for treatment failure. Cytotoxic gold compounds hold great promise to reach this goal; however, their modes of action are still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2-DE and MS analysis to identify differential protein expression in a cisplatin-resistant human ovarian cancer cell line (A2780/R) following treatment with two representative gold compounds, namely Auranofin and Auoxo6. It is shown that Auranofin mainly acts by altering the expression of Proteasome proteins while Auoxo6 mostly modifies proteins related to mRNA splicing, trafficking and stability. We also found that Thioredoxin-like protein 1 expression is greatly reduced after treatment with both gold compounds. These results are highly indicative of the likely sites of action of the two tested gold drugs and of the affected cellular functions. The implications of the obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold agents.

Item Type:Article
ID Code:7286
Status:Published
Refereed:Yes
Uncontrolled Keywords:Cytotoxicity, gold compounds, proteomic analysis
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
Publisher:Royal Society of Chemistry
eISSN:1756-591X
Deposited On:23 Mar 2012 11:14

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