Details

Autor(en) / Beteiligte

• Magherini, Francesca
• Fiaschi, Tania
• Valocchia, Elisa
• Becatti, Matteo
• Pratesi, Alessandro
• Marzo, Tiziano
• Massai, Lara
• Gabbiani, Chiara
• Landini, Ida
• Nobili, Stefania
• Mini, Enrico
• Messori, Luigi
• Modesti, Alessandra
• Gamberi, Tania

Titel

Antiproliferative effects of two gold(I)-N-heterocyclic carbene complexes in A2780 human ovarian cancer cells: a comparative proteomic study

Ist Teil von

• Oncotarget, 2018-06, Vol.9 (46), p.28042-28068

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Au(NHC) and Au(NHC) , a monocarbene gold(I) complex and the corresponding bis(carbene) complex, are two structurally related compounds, endowed with cytotoxic properties against several cancer cell lines. Herein, we explore the molecular and cellular mechanisms at the basis of their cytotoxicity in A2780 human ovarian cancer cells. Through a comparative proteomic analysis, we demonstrated that the number of modulated proteins is far larger in Au(NHC) -treated than in Au(NHC)-treated A2780 cells. Both gold compounds mainly affected proteins belonging to the following functional classes: protein synthesis, metabolism, cytoskeleton and stress response and chaperones. Particularly, Au(NHC) gave rise to an evident upregulation of several glycolytic enzymes. Moreover, only Au(NHC) triggered a net impairment of respiration and a metabolic shift towards glycolysis, suggesting that mitochondria are relevant cellular targets. We also found that both carbenes, similarly to the gold(I) compound auranofin, caused a strong inhibition of the seleno-enzyme thioredoxin reductase (TrxR). In conclusion, we highlighted that coordination of two carbene ligands to the same gold(I) center greatly enhances the antiproliferative effects of the resulting compound in comparison to the monocarbene derivative. Moreover, TrxR inhibition and metabolic impairment seem to play a major role in the Au(NHC) cytotoxicity. Overall, these antiproliferative effects were also confirmed on other two human ovarian cancer cell lines ( SKOV3 and IGROV1).