Epothilone B induces glioblastoma cell death via survivin down-regulation

Exp Oncol. 2008 Sep;30(3):195-201.


Aim: The clinical resistance of glioblastomas to chemotherapeutic agents can be attributed to drug efflux pumps, such as P-glycoprotein, which contributes to reduce drug efficacy. The present study examined the utility of epothilone B, which is not a substrate for P-glycoprotein, on glioblastoma cells.

Methods: In vitro methods with glioblastoma cells varying in p53 status were used to assess the efficacy of epothilone B to induce anti-neoplastic responses. Immunofluorescence and ELISA procedures were used to examine levels of tubulin and survivin in epothilone B treated glioblastoma cells, while acridine orange labeling was used to detect the mode of epothilone B induced cell death.

Results: A clinically achievable concentration of epothilone B induced a cytotoxic response in p53 mutant glioblastoma cells, as a consequence of survivin down-regulation and tubulin redistribution, while a cytostatic response was observed in p53 null glioblastoma cells with a modest increase in survivin expression post-epothilone B treatment. However, p53 wild-type glioblastoma cells did not sustain a positive anti-tumorigenic response to epothilone B.

Conclusion: Epothilone B, induced positive differential responses in glioblastoma cells with abnormal p53 status, but not in p53 wild-type cells. This suggests that epothilone B is a potential alternative to classic microtubule inhibiting agents (ie vincristine, paclitaxel) used to treat clinical glioblastomas with p53 mutations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Proliferation
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Epothilones / pharmacology*
  • Fluorescent Antibody Technique
  • Gentian Violet
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / metabolism
  • Mutation / genetics
  • Neoplasm Proteins / metabolism
  • Survivin
  • Tubulin / metabolism
  • Tubulin Modulators / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • BIRC5 protein, human
  • Epothilones
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • TP53 protein, human
  • Tubulin
  • Tubulin Modulators
  • Tumor Suppressor Protein p53
  • Gentian Violet
  • epothilone B