Combined Applications of Repurposed Drugs and Their Detrimental Effects on Glioblastoma Cells

Anticancer Res. 2019 Jan;39(1):207-214. doi: 10.21873/anticanres.13099.


Background/aim: Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM.

Materials and methods: Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system.

Results: The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole.

Conclusion: These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.

Keywords: Glioblastoma cells; cell death; combined treatment; proliferation; standard of care treatment.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glycoproteins / genetics*
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Riluzole / administration & dosage
  • Temozolomide / administration & dosage
  • Tranylcypromine / administration & dosage
  • Valproic Acid / administration & dosage
  • Xenograft Model Antitumor Assays


  • Glycoproteins
  • tissue-factor-pathway inhibitor 2
  • Tranylcypromine
  • Valproic Acid
  • Riluzole
  • Temozolomide