Article

Journal of Neuro-Oncology

, Volume 67, Issue 1, pp 65-73

Neurotoxicity of Platinum Compounds: Comparison of the Effects of Cisplatin and Oxaliplatin on the Human Neuroblastoma Cell Line SH-SY5Y

  • Elisabetta DonzelliAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Maria CarfìAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Mariarosaria MilosoAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Alberto StradaAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Stefania GalbiatiAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Martine BayssasAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Genevieve Griffon-EtienneAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca
  • , Guido CavalettiAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-BicoccaClinica Neurologica, Ospedale San Gerardo
  • , Maria Grazia PetruccioliAffiliated withDipartimento di Anatomia Umana, Universit`a degli Studi di Milano
    • , Giovanni TrediciAffiliated withDipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The main dose-limiting side effect of cancer treatment with platinum compounds is peripheral neurotoxicity. To investigate the intracellular mechanisms of platinum drugs neurotoxicity we have studied the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y. Both platinum compounds are toxic causing cellular death by inducing apoptosis but oxaliplatin is less neurotoxic than cisplatin. The study of the proteins involved in the intracellular transduction pathways that may cause apoptotic death, revealed a very similar pattern of changes after exposure to cisplatin or oxaliplatin. In particular, as demonstrated by densitometric analysis, after exposure to both platinum compounds the total amount of the anti-apoptotic protein Bcl-2 was significantly reduced. Conversely, the amount of the pro-apoptotic protein p53 significantly increased. Caspases 3 and 7 were activated, but their activation was a late event, indicating a secondary role in the apoptotic process. Among the mitogen activated protein kinases, only the p38 protein was activated (phosphorylated) early enough to have a possible role in inducing apoptosis, possibly through p53 stabilization. The results of the present study and the data of the literature demonstrate that the ways in which cisplatin and oxaliplatin are neurotoxic are very similar and include not only DNA damage, but also the modulation of specific molecules involved in regulating the cellular equilibrium between apoptotic death and the cell cycle.

apoptosis Bcl-2 caspase cisplatin MAPK oxaliplatin p53 SH-SY5Y cells