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2D-DIGE analysis of ovarian cancer cell responses to cytotoxic gold compounds

Guidi, Francesca and Puglia, Michele and Gabbiani, Chiara and Landini, Ida and Gamberi, Tania and Fregona, Dolores and Cinellu, Maria Agostina and Nobili, Stefania and Mini, Enrico and Bini, Luca and Modesti, Pietro Amedeo and Modesti, Alessandra and Messori, Luigi (2012) 2D-DIGE analysis of ovarian cancer cell responses to cytotoxic gold compounds. Molecular BioSystems, Vol. 8 (4), p. 985-993. eISSN 1742-2051. Article.

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DOI: 10.1039/C1MB05386H

Abstract

Cytotoxic gold compounds hold today great promise as new pharmacological agents for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2D-DIGE analysis to identify differential protein expression in a cisplatin-sensitive human ovarian cancer cell line (A2780/S) following treatment with two representative gold(III) complexes that are known to be potent antiproliferative agents, namely AuL12 and Au2Phen. Software analysis using DeCyder was performed and few differentially expressed protein spots were visualized between the three examined settings after 24 h exposure to the cytotoxic compounds, implying that cellular damage at least during the early phases of exposure is quite limited and selective, reflecting the attempts of the cell to repair damage and to survive the insult. The potential of novel proteomic methods to disclose mechanistic details of cytotoxic metallodrugs is herein further highlighted. Different patterns of proteomic changes were highlighted for the two metallodrugs with only a few perturbed protein spots in common. Using MALDI-TOF MS and ESI-Ion trap MS/MS, several differentially expressed proteins were identified. Two of these were validated by western blotting: Ubiquilin-1, responsible for inhibiting degradation of proteins such as p53 and NAP1L1, a candidate marker identified in primary tumors. Ubiquilin-1 resulted over-expressed following both treatments and NAP1L1 was down-expressed in AuL12-treated cells in comparison with control and with Au2Phen-treated cells. In conclusion, we performed a comprehensive analysis of proteins regulated by AuL12 and Au2Phen, providing a useful insight into their mechanisms of action.

Item Type:Article
ID Code:7328
Status:Published
Refereed:Yes
Uncontrolled Keywords:Mass-spectrometry, gold compounds, 2D-DIGE
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:1742-2051
Deposited On:04 Apr 2012 14:02

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