The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines

  • Authors:
    • S. Schweyer
    • A. Soruri
    • A. Heintze
    • H. J. Radzun
    • A. Fayyazi
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1671
  • Pages: 1671-1676
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Abstract

Testicular germ cell tumours (TGCT) are the most common solid tumour among young males. Whereas in 1970s, only 5% of patients with a metastatic testicular tumours survived their disease, these days 80% of patients treated by modern cisdiamminedichloroplatinum (cisplatin, CDDP)-based chemotherapy are cured. Although data are accumulating on the effect of the mitogen-activated protein kinase (MAPK) family on the CDDP-induced apoptosis in tumour cells, the mechanisms by which CDDP initiates apoptosis in TGCT are not completely understood. Applying Western blot and phosphorylated kinase-specific ELISA analyses, flow cytometry, blocking experiments, and morphological methods we sought here to define the MAPK pathway(s) involved in the CDDP-induced apoptosis in the human TGCT cell line NCCIT. Our experiments showed that within hours of CDDP application only the extracellular signal-regulated kinase (ERK) was dually phosphorylated and caspase-3 became active. Functional assays using chemical inhibitors demonstrated that the phosphorylation of ERK was mediated by reactive oxygen species in an Raf-1-independent manner and required the activation of caspase-3. Thus, our data suggest that CDDP mediates its apoptosis-inducing effect on the human malignant testicular germ cells, at least partially, through activation of the MEK-ERK signaling pathway in a ROS-dependent, Raf-1-independent manner.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Schweyer S, Soruri A, Heintze A, Radzun HJ and Fayyazi A: The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines. Int J Oncol 25: 1671-1676, 2004
APA
Schweyer, S., Soruri, A., Heintze, A., Radzun, H.J., & Fayyazi, A. (2004). The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines. International Journal of Oncology, 25, 1671-1676. https://doi.org/10.3892/ijo.25.6.1671
MLA
Schweyer, S., Soruri, A., Heintze, A., Radzun, H. J., Fayyazi, A."The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines". International Journal of Oncology 25.6 (2004): 1671-1676.
Chicago
Schweyer, S., Soruri, A., Heintze, A., Radzun, H. J., Fayyazi, A."The role of reactive oxygen species in cisplatin-induced apoptosis in human malignant testicular germ cell lines". International Journal of Oncology 25, no. 6 (2004): 1671-1676. https://doi.org/10.3892/ijo.25.6.1671