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Updated: Feb 17, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
Selection and characterization of a human ovarian cancer cell line resistant to auranofin
Ida Landini1, Andrea Lapucci1, Alessandro Pratesi2
1Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy.
Abstract:
The anti-arthritic drug auranofin exerts also potent antitumour activity in in vitro and in vivo models, whose mechanisms are not yet well defined. From an auranofin-sensitive human ovarian cancer cell line A2780, a highly resistant (>20-fold) subline (A2780/AF-R) was developed and characterized. Marked reduction of gold accumulation occurred in auranofin-resistant A2780 cells. Also, moderately higher thioredoxin reductase activity in A2780/AF-R cells was observed while no changes in intracellular glutathione content occurred. Resistance to auranofin was associated with a low level of cross-resistance to some investigational gold compounds as well as to oxaliplatin and other anticancer drugs with different mode of action (i.e. melphalan, vinblastine, doxorubicin, etoposide, and paclitaxel). Reduced gold accumulation was associated to substantial gene expression changes in various influx (e.g. SLC22A1, SLC47A1, SLCO1B1) and efflux (e.g. ABCB1, ABCC2, ABCC3) transporters. The expression levels of selected proteins (i.e. SLC22A1, SLC47A1, P-gp) were also changed accordingly. These data provide evidence that multiple drug transporters may act as mediators of transport of auranofin and other gold compounds in cancer cells. Further investigation into the molecular mechanisms mediating transport of auranofin and new gold complexes in view of their potential clinical application in the treatment of cancer is warranted.
Insights
Auranofin, an anti-arthritic drug, shows anticancer effects. Resistance in ovarian cancer cells involves reduced gold uptake and altered drug transporters, suggesting their role in auranofin
Area of Science:
- Pharmacology
- Cancer Biology
- Drug Resistance Mechanisms
Background:
- Auranofin, an anti-arthritic medication, demonstrates significant anticancer properties in preclinical models.
- The precise mechanisms underlying auranofin's antitumour activity and the development of resistance remain incompletely understood.
Purpose of the Study:
- To investigate the mechanisms of auranofin resistance in human ovarian cancer cells.
- To characterize the molecular changes associated with acquired resistance to auranofin.
Main Methods:
- Development and characterization of auranofin-resistant human ovarian cancer cell line (A2780/AF-R).
- Assessment of gold accumulation, thioredoxin reductase activity, and glutathione content.
- Analysis of gene and protein expression of drug transporters (influx and efflux).
Main Results:
- Auranofin-resistant cells exhibited significantly reduced gold accumulation and moderate increases in thioredoxin reductase activity.
- Cross-resistance was observed with other gold compounds and certain unrelated anticancer drugs.
- Gene expression analysis revealed significant alterations in influx and efflux drug transporter genes (e.g., SLC22A1, ABCB1).
Conclusions:
- Drug transporters play a crucial role in mediating the transport of auranofin and related gold compounds in cancer cells.
- Understanding these transporter mechanisms is essential for the potential clinical application of auranofin and new gold-based anticancer therapies.
