New methods of isolation of olive secoiridoids and systematic study of their anti-proliferative/cytotoxic effect on multiple cancer cell lines

Olive oil phenols (OOPs: oleocanthal, oleacein, oleuropein aglycone and ligstroside aglycone), have been associated with the prevention of many types of human cancers. Previous studies have demonstrated that certain of these compounds inhibit cell proliferation and induce apoptosis. However, there is no systematic study of all the compounds under the same conditions due to the difficulties related to their isolation in pure form. We have developed new methods for large-scale selective extraction of these compounds [1], [2], making them affordable for detailed investigation. One step extraction of olive leaves using cold water and EtOAc permitted isolation of oleacein in 95% purity without chromatography. Similarly, extraction of intact olive leaves with dichloromethane permitted isolation of pure oleomissional without chromatography. Alkaline treatment of oleomissional led quantitatively to oleuropein aglycon. Finally, water extraction of olive oil led to pure oleocanthal that was further oxidized to oleocanthalic acid. All the pure compounds as well as their combinations were assessed for their cytotoxic action on sixteen human cancer cell lines. EC₅₀ values were calculated for each isolated compound and their cytotoxic/anti-proliferative effect were estimated when different OOPs were combined. Finally, olive oil extracts of determined OOPsʼ content were tested. It was demonstrated that all OOPs impair cancer cell viability in a dose and time dependent manner in all cancer cells, while oleocanthal (EC₅₀ = 9 μM) was the most effective in all cancer cell lines. Most combinations of OOPs showed strong synergistic effect, whereas OOPsʼ extracts strongly impaired tumour cell viability even in the most resistant cancer cell lines.

Publication History

Article published online:
12 December 2022

• References

• 1 Melliou E, Magiatis P, Diamantakos P, Rigakou A. Method for obtaining of oleacein and oleomissional secoiridoids and method of producing pharmaceutical preparations thereof. WO2020165613.
• 2 Melliou E, Magiatis P, Diamantakos P, Rigakou A. Method for obtaining of oleocanthal secoiridoids and method for producing respective pharmaceutical preparations. WO2020165614.