In vitro antitumour activity and cellular pharmacological properties of the platinum-iminoether complex trans-[PtCl2[E-HN=C(OMe)Me]2]

Int J Oncol. 1999 Nov;15(5):1039-44. doi: 10.3892/ijo.15.5.1039.

Abstract

The platinum complex trans-[PtCl2¿E-HN=C(OMe)Me¿2] was compared to cisplatin for cytotoxicity towards tumour cells, and for cellular pharmacological properties in A2780 and cisplatin-resistant A2780/Cp8 ovarian cancer cells. Trans-[PtCl2¿E-HN=C(OMe)Me¿2] was comparably cytotoxic to cisplatin (mean IC50 after 72 h exposure = 6. 1 microM and 7 microM, respectively) and did not show cross-resistance in A2780/Cp8 cells (resistance factor = 0.9). Cellular accumulation measurements after treatment with equimolar drug concentrations showed that trans-[PtCl2¿E-HN=C(OMe)Me¿2] entered both A2780 and A2780/Cp8 cells much more efficiently than cisplatin, whose accumulation was reduced in A2780/Cp8 cells. Unlike cisplatin, trans-[PtCl2¿E-HN=C(OMe)Me¿2] induced rapidly cell death and cell cycle modifications of treated cells, thus indicating substantially different mechanistic properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / toxicity*
  • Biological Transport
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cisplatin / pharmacokinetics
  • Cisplatin / toxicity
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / toxicity*
  • Ovarian Neoplasms
  • Platinum / pharmacokinetics
  • Platinum / toxicity
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • dichloroplatinum(E-iminoether)2
  • Platinum
  • Cisplatin