Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds.
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.
Department of Biochemical Sciences, University of Florence, viale G. Morgagni, 50, 50134 Firenze, Italy.
Francesca
F
Guidi
Ida
I
Landini
Michele
M
Puglia
Francesca
F
Magherini
Chiara
C
Gabbiani
Maria Agostina
MA
Cinellu
Stefania
S
Nobili
Tania
T
Fiaschi
Luca
L
Bini
Enrico
E
Mini
Luigi
L
Messori
Alessandra
A
Modesti
D001310:Auranofin / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017612:Gold Compounds / Q000494:pharmacology*; D006801:Humans; D013058:Mass Spectrometry; D010051:Ovarian Neoplasms / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
D017612:Gold Compounds; D001310:Auranofin