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November 2012 Volume 28 Issue 5

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Article

17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion

  • Authors:
    • Katarzyna Miekus
    • Jacek Kijowski
    • Małgorzata Sekuła
    • Marcin Majka
  • View Affiliations / Copyright

    Affiliations: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University School of Medicine, Cracow, Poland
  • Pages: 1903-1903
    |
    Published online on: August 27, 2012
       https://doi.org/10.3892/or.2012.1996
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Abstract

Glioblastoma multiforme (GBM) is the most frequent and the most malignant human brain tumor. The expression of receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) is strongly increased in GBM, where they promote tumor proliferation, cell survival, migration, invasion and angiogenesis. We used geldanamycins (GAs) (inhibitors of HSP90) in order to block glioblastoma growth and HGF-dependent cell migration and invasion. The effect of GAs on three GBM cell lines was tested and we found their antiproliferative effect on tumor cells. The maximum level of inhibition reached 70%. After treatment with GAs, cells also became apoptotic as determined by Annexin V-positive staining and activation of the caspase-3 pathway. We examined the expression and activity of the MET receptor on GBM cell lines and we observed phosphorylation of AKT and MAPK after HGF stimulation by western blot analysis. Since GBM cells express high level of MET receptor and were shown to respond to HGF by increased motility we tested if GAs could negatively affect GBM cell movement. In our study, we found that GAs inhibited the chemotaxis of glioblastoma cells toward the hepatocyte growth factor gradient. The GAs also blocked migration of tumor cells through a Matrigel layer in invasion assays. The strongest inhibitory effect was observed for GA and its analog, 17AEP-GA. Based on our results, GAs, particularly 17AEP-GA, could be considered as a new potential agent to treat glioblastoma multiforme.
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Copy and paste a formatted citation
Spandidos Publications style
Miekus K, Kijowski J, Sekuła M and Majka M: 17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. Oncol Rep 28: 1903-1903, 2012.
APA
Miekus, K., Kijowski, J., Sekuła, M., & Majka, M. (2012). 17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. Oncology Reports, 28, 1903-1903. https://doi.org/10.3892/or.2012.1996
MLA
Miekus, K., Kijowski, J., Sekuła, M., Majka, M."17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion". Oncology Reports 28.5 (2012): 1903-1903.
Chicago
Miekus, K., Kijowski, J., Sekuła, M., Majka, M."17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion". Oncology Reports 28, no. 5 (2012): 1903-1903. https://doi.org/10.3892/or.2012.1996
Copy and paste a formatted citation
x
Spandidos Publications style
Miekus K, Kijowski J, Sekuła M and Majka M: 17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. Oncol Rep 28: 1903-1903, 2012.
APA
Miekus, K., Kijowski, J., Sekuła, M., & Majka, M. (2012). 17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. Oncology Reports, 28, 1903-1903. https://doi.org/10.3892/or.2012.1996
MLA
Miekus, K., Kijowski, J., Sekuła, M., Majka, M."17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion". Oncology Reports 28.5 (2012): 1903-1903.
Chicago
Miekus, K., Kijowski, J., Sekuła, M., Majka, M."17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion". Oncology Reports 28, no. 5 (2012): 1903-1903. https://doi.org/10.3892/or.2012.1996
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