Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells

J Clin Invest. 1995 Mar;95(3):1193-8. doi: 10.1172/JCI117768.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anions / pharmacology
  • Antimony Potassium Tartrate / pharmacology*
  • Antimony Potassium Tartrate / toxicity
  • Arsenites / metabolism
  • Arsenites / pharmacology*
  • Arsenites / toxicity
  • Biological Transport
  • Carcinoma
  • Cisplatin / pharmacology*
  • Cisplatin / toxicity
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple / physiology*
  • Female
  • Head and Neck Neoplasms
  • Humans
  • Neoplasms / drug therapy*
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / pharmacology
  • Ovarian Neoplasms
  • Selection, Genetic
  • Tumor Cells, Cultured


  • Anions
  • Arsenites
  • Organoplatinum Compounds
  • platinum ethylenediamine dichloride
  • Antimony Potassium Tartrate
  • arsenite
  • Cisplatin