Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells
Related Experiment Video
Updated: Apr 14, 2026
Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
P Naredi1, D D Heath, R E Enns
1Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Abstract:
Cross-resistance between cisplatin (DDP) and metalloid salts in human cells was sought on the basis that mechanisms that mediate metalloid salt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP resistance were found to be cross-resistant to antimony potassium tartrate, which contains trivalent antimony. The DDP-resistant variant 2008/A was also cross-resistant to arsenite but not to stibogluconate, which contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. Resistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was greater (17-fold), irrespective of whether the cells were selected by exposure to DDP or to antimony potassium tartrate. In the resistant sublines, uptake of [3H]-dichloro(ethylenediamine) platinum(II) was reduced to 41-52% of control, and a similar deficit was observed in the accumulation of arsenite. We conclude that DDP, antimony potassium tartrate, and arsenite all share a common mechanism of resistance in human cells and that this is due in part to an accumulation defect.
Insights
Cisplatin (DDP) and certain metalloid salts like antimony potassium tartrate and arsenite share a common resistance mechanism in human cancer cells. This cross-resistance is partly due to reduced cellular accumulation of these compounds.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Mechanisms of drug resistance can be conserved across species.
- Metalloid salts and platinum-based drugs are used in cancer therapy.
Purpose of the Study:
- To investigate cross-resistance between cisplatin (DDP) and metalloid salts in human cancer cell lines.
- To explore shared resistance mechanisms between DDP and trivalent/pentavalent antimony compounds, and arsenite.
Main Methods:
- Developing DDP-resistant and antimony potassium tartrate-resistant human carcinoma cell lines.
- Assessing cross-resistance profiles to various metalloid salts.
- Measuring cellular uptake of DDP and arsenite in resistant and sensitive cells.
Main Results:
- DDP-resistant cell lines exhibited cross-resistance to antimony potassium tartrate and arsenite, but not pentavalent antimony.
- Antimony potassium tartrate-resistant cells were cross-resistant to DDP and arsenite.
- Reduced cellular accumulation of DDP and arsenite was observed in resistant sublines.
Conclusions:
- Cisplatin, antimony potassium tartrate, and arsenite share a common resistance mechanism in human cells.
- This shared resistance is partly attributed to defects in cellular accumulation.
- Understanding these mechanisms could inform cancer treatment strategies.
