Proteomic analysis of A2780/S ovarian cancer cell response to the cytotoxic organogold(III) compound Aubipy(c).
Aubipyc is an organogold(III) compound endowed with encouraging anti-proliferative properties in vitro that is being evaluated pre-clinically as a prospective anticancer agent. A classical proteomic approach is exploited here to elucidate the mechanisms of its biological actions in A2780 human ovarian cancer cells. Based on 2-D gel electrophoresis separation and subsequent mass spectrometry identification, a considerable number of differentially expressed proteins were highlighted in A2780 cancer cells treated with Aubipyc. Bioinformatic analysis of the groups of up-regulated and down-regulated proteins pointed out that Aubipyc primarily perturbs mitochondrial processes and the glycolytic pathway. Notably, some major alterations in the glycolytic pathway were validated through Western blot and metabolic investigations.


CONCLUSIONS
This is the first proteomic analysis regarding Aubipyc cytotoxicity in A2780/S ovarian cancer cell line. Aubipyc is a promising gold(III) compound which manifests an appreciable cytotoxicity toward the cell line A2780, being able to overcome resistance to platinum. The proteomic study revealed for Aubipyc different cellular alterations with respect to cisplatin as well as to other gold compound such as auranofin. Remarkably, the bioinformatic analysis of proteomic data pointed out that Aubipyc treatment affected, directly or indirectly, several glycolytic enzymes. These data suggest a new mechanism of action for this gold drug and might have an impact on the use of gold-based drug in cancer treatment.
Department of Clinical and Preclinical Biomedical Sciences, University of Florence, Italy.
Tania
T
Gamberi
Department of Chemistry, University of Florence, Italy.
Lara
L
Massai
Department of Clinical and Preclinical Biomedical Sciences, University of Florence, Italy.
Francesca
F
Magherini
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Italy.
Ida
I
Landini
Department of Clinical and Preclinical Biomedical Sciences, University of Florence, Italy.
Tania
T
Fiaschi
Department of Chemistry, University of Florence, Italy.
Federica
F
Scaletti
Department of Chemistry and Industrial Chemistry, University of Pisa, Italy.
Chiara
C
Gabbiani
Functional Proteomic Section, Department of Life Sciences, University of Siena, Italy.
Laura
L
Bianchi
Functional Proteomic Section, Department of Life Sciences, University of Siena, Italy.
Luca
L
Bini
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Italy.
Stefania
S
Nobili
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Italy.
Gabriele
G
Perrone
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Italy.
Enrico
E
Mini
Department of Chemistry, University of Florence, Italy. Electronic address: luigi.messori@unifi.it.
Luigi
L
Messori
Department of Clinical and Preclinical Biomedical Sciences, University of Florence, Italy. Electronic address: alessandra.modesti@unifi.it.
Alessandra
A
Modesti
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D050607:Organogold Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
D000970:Antineoplastic Agents; D050607:Organogold Compounds; C453480:hydroxo(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)gold(III); D015082:2,2'-Dipyridyl
Cancer; Gold compounds; Proteomics; Two-dimensional electrophoresis