Anticancer Potential of Oleuropein, the Polyphenol of Olive Oil, With 2-Methoxyestradiol, Separately or in Combination, in Human Osteosarcoma Cells

Anticancer Res. 2019 Mar;39(3):1243-1251. doi: 10.21873/anticanres.13234.


Background/aim: Oleuropein belongs to the potent polyphenols of olive oil. Notably, it is considered as a potentially active anticancer agent. Herein, the anticancer efficiency of oleuropein, when used separately and in combination with the chemotherapeutic agent, 2-methoxyestradiol (2-ME), was investigated in highly metastatic osteosarcoma (OS) cells.

Materials and methods: Human OS cells (143B OS cell line) were incubated with oleuropein and 2-ME, alone or in combination. Cell viability was determined by the MTT assay. Cell migration assays were used in order to determine the anti-migratory potential of the compounds, while their impact on autophagy was evaluated via the LC3-antibody-based detection assay. The interaction between oleuropein and 2-ME was determined via the CalcuSyn software.

Results: Both anti-migratory and anti-proliferative effects of oleuropein were demonstrated on human OS cells. Anticancer effects of oleuropein were significantly enhanced after 2-ME addition. Treatment of 143B OS cell with oleuropein, alone or in combination with 2-ME resulted in induction of autophagy.

Conclusion: The obtained data suggest an anticancer effect of oleuropein, alone and in combination with 2-ME, on highly metastatic 143B OS cells. Notably, a synergism between oleuropein and 2-ME towards 143B OS cells was detected. The exact mechanism of this synergism needs to be further investigated; nonetheless, induction of nitro-oxidative stress and/or induction of autophagy are suggested.

Keywords: 2-methoxyestradiol; Oleuropein; autophagy; cell death; cell migration; osteosarcoma.

MeSH terms

  • 2-Methoxyestradiol / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Bone Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Drug Synergism
  • Humans
  • Iridoid Glucosides
  • Iridoids / pharmacology*
  • Olive Oil
  • Osteosarcoma / drug therapy*


  • Antineoplastic Agents
  • Iridoid Glucosides
  • Iridoids
  • Olive Oil
  • oleuropein
  • 2-Methoxyestradiol