Journal of Neuro-Oncology

, Volume 67, Issue 1–2, pp 65–73 | Cite as

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

  • Elisabetta Donzelli
  • Maria Carfì
  • Mariarosaria Miloso
  • Alberto Strada
  • Stefania Galbiati
  • Martine Bayssas
  • Genevieve Griffon-Etienne
  • Guido Cavaletti
  • Maria Grazia Petruccioli
  • Giovanni Tredici

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 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Elisabetta Donzelli
    • 1
  • Maria Carfì
    • 1
  • Mariarosaria Miloso
    • 1
  • Alberto Strada
    • 1
  • Stefania Galbiati
    • 1
  • Martine Bayssas
    • 2
  • Genevieve Griffon-Etienne
    • 2
  • Guido Cavaletti
    • 1
    • 3
  • Maria Grazia Petruccioli
    • 4
  • Giovanni Tredici
    • 1
  1. 1.Dipartimento di Neuroscienze e Tecnologie BiomedicheUniversità degli Studi di Milano-BicoccaMonzaItaly
  2. 2.Dipartimento di Neuroscienze e Tecnologie BiomedicheUniversità degli Studi di Milano-BicoccaMonzaItaly
  3. 3.Clinica NeurologicaOspedale San GerardoMonzaItaly
  4. 4.Dipartimento di Anatomia UmanaUniversit`a degli Studi di MilanoMilanoItaly

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