Comparative analysis of cell injury after exposure to antitumor platinum derivatives in kidney tubular epithelial cells

Chemotherapy. 2008;54(3):217-23. doi: 10.1159/000140465. Epub 2008 Jun 18.


Background: Platinum derivatives differ in effectiveness and safety. The purpose of this study is to compare differences in the mechanism of nephrotoxicity among these derivatives.

Methods: LLC-PK(1) cells were used as a model of tubular epithelial cells. Cytotoxicity was evaluated by WST-1 assay, and cellular accumulation of platinum was examined by inductively coupled plasma mass spectrometer. As indexes of necrosis and apoptosis, lactate dehydrogenase release, DNA fragmentation and caspase 3 activation were examined.

Results: In terms of cytotoxicity, the derivatives ranked in the order of oxaliplatin > cisplatin > nedaplatin > carboplatin, being comparable with that for the level of platinum accumulated in LLC-PK(1) cells. Lactate dehydrogenase release and DNA fragmentation were observed following treatment with all the derivatives, but were lowest for carboplatin. In terms of activating caspase 3, the order was cisplatin > nedaplatin > oxaliplatin > carboplatin.

Conclusion: Cytotoxicity by the derivatives was dependent on cellular accumulation of platinum and suggested to be mediated by apoptosis and necrosis; however, contributions differed among the derivatives.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Cell Shape / drug effects
  • Enzyme Activation / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Hydro-Lyases / metabolism
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology*
  • Platinum / chemistry
  • Platinum / metabolism
  • Platinum / pharmacology*
  • Swine


  • Antineoplastic Agents
  • Platinum
  • Caspase 3
  • Hydro-Lyases
  • lactate dehydratase