Cisplatin-resistance involves the defective processing of MEKK1 in human ovarian adenocarcinoma 2008/C13 cells.

  • Authors:
    • G Gebauer
    • B Mirakhur
    • Q Nguyen
    • S K Shore
    • H Simpkins
    • N Dhanasekaran
  • View Affiliations

  • Published online on: February 1, 2000     https://doi.org/10.3892/ijo.16.2.321
  • Pages: 321-326
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Abstract

Cisplatin has been widely used as a chemotherapeutic agent to treat different types of tumors. However, its use is limited by the ability of the tumor cells to develop cisplatin-resistance. The molecular lesion that produces cisplatin-resistance is poorly understood. In this report, we show that cisplatin activates a robust apoptotic pathway involving the activation of JNK and p38MAPK whereas it fails to elicit such a response in cisplatin-resistant 2008/C13 cells. Analysis of the defective apoptotic pathway in 2008/C13 cells indicates that these cells are deficient in the proteolytic activation of MEKK1 by caspase-3. The blunted activity of caspase-3 appears to be closely related to the increased levels of the anti-apoptotic protein Bcl-xL seen in the resistant cells. These studies, for the first time, demonstrate that inadequate caspase-3 processing and MEKK1 activation can lead to a drug-resistant phenotype.

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February 2000
Volume 16 Issue 2

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

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APA
Gebauer, G., Mirakhur, B., Nguyen, Q., Shore, S., Simpkins, H., & Dhanasekaran, N. (2000). Cisplatin-resistance involves the defective processing of MEKK1 in human ovarian adenocarcinoma 2008/C13 cells.. International Journal of Oncology, 16, 321-326. https://doi.org/10.3892/ijo.16.2.321
MLA
Gebauer, G., Mirakhur, B., Nguyen, Q., Shore, S., Simpkins, H., Dhanasekaran, N."Cisplatin-resistance involves the defective processing of MEKK1 in human ovarian adenocarcinoma 2008/C13 cells.". International Journal of Oncology 16.2 (2000): 321-326.
Chicago
Gebauer, G., Mirakhur, B., Nguyen, Q., Shore, S., Simpkins, H., Dhanasekaran, N."Cisplatin-resistance involves the defective processing of MEKK1 in human ovarian adenocarcinoma 2008/C13 cells.". International Journal of Oncology 16, no. 2 (2000): 321-326. https://doi.org/10.3892/ijo.16.2.321