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Article

Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells

  • Authors:
    • Alejandro Urdiciain
    • Elena Erausquin
    • Bárbara Meléndez
    • Juan A. Rey
    • Miguel A. Idoate
    • Javier S. Castresana
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain, Molecular Pathology Research Unit, Virgen de la Salud Hospital, 45071 Toledo, Spain, IdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, Spain, Department of Pathology, University of Navarra Clinic, 31008 Pamplona, Spain
  • Pages: 1797-1808
    |
    Published online on: March 1, 2019
       https://doi.org/10.3892/ijo.2019.4739
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Abstract

Glioblastoma or grade IV astrocytoma is the most common and lethal form of glioma. Current glioblastoma treatment strategies use surgery followed by chemotherapy with temozolomide. Despite this, numerous glioblastoma cases develop resistance to temozolomide treatments, resulting in a poor prognosis for the patients. Novel approaches are being investigated, including the inhibition of histone deacetylase 6 (HDAC6), an enzyme that deacetylates α‑tubulin, and whose overexpression in glioblastoma is associated with the loss of primary cilia. The aim of the present study was to treat glioblastoma cells with a selective HDAC6 inhibitor, tubastatin A, to determine if the malignant phenotype may be reverted. The results demonstrated a notable increase in acetylated α‑tubulin levels in treated cells, which associated with downregulation of the sonic hedgehog pathway, and may hypothetically promote ciliogenesis in those cells. Treatment with tubastatin A also reduced glioblastoma clonogenicity and migration capacities, and accelerated temozolomide‑induced apoptosis. Finally, HDAC6 inhibition decreased the expression of mesenchymal markers, contributing to reverse epithelial‑mesenchymal transition in glioblastoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Urdiciain A, Erausquin E, Meléndez B, Rey JA, Idoate MA and Castresana JS: Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells. Int J Oncol 54: 1797-1808, 2019.
APA
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J.A., Idoate, M.A., & Castresana, J.S. (2019). Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells. International Journal of Oncology, 54, 1797-1808. https://doi.org/10.3892/ijo.2019.4739
MLA
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells". International Journal of Oncology 54.5 (2019): 1797-1808.
Chicago
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells". International Journal of Oncology 54, no. 5 (2019): 1797-1808. https://doi.org/10.3892/ijo.2019.4739
Copy and paste a formatted citation
x
Spandidos Publications style
Urdiciain A, Erausquin E, Meléndez B, Rey JA, Idoate MA and Castresana JS: Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells. Int J Oncol 54: 1797-1808, 2019.
APA
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J.A., Idoate, M.A., & Castresana, J.S. (2019). Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells. International Journal of Oncology, 54, 1797-1808. https://doi.org/10.3892/ijo.2019.4739
MLA
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells". International Journal of Oncology 54.5 (2019): 1797-1808.
Chicago
Urdiciain, A., Erausquin, E., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."Tubastatin A, an inhibitor of HDAC6, enhances temozolomide‑induced apoptosis and reverses the malignant phenotype of glioblastoma cells". International Journal of Oncology 54, no. 5 (2019): 1797-1808. https://doi.org/10.3892/ijo.2019.4739
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