Oleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract

Hum Exp Toxicol. 2019 Sep;38(9):1102-1110. doi: 10.1177/0960327119855123. Epub 2019 Jun 6.


Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey's post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2-ΔCt method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.

Keywords: Glioblastoma multiforme; oleuropein; temozolomide.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Glioblastoma / genetics*
  • Humans
  • Iridoid Glucosides
  • Iridoids / pharmacology*
  • MicroRNAs*
  • Olea*
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Temozolomide / pharmacology


  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Iridoid Glucosides
  • Iridoids
  • MicroRNAs
  • Plant Extracts
  • oleuropein
  • Temozolomide