Preprint Article Version 1 This version is not peer-reviewed

Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies

Version 1 : Received: 9 November 2018 / Approved: 12 November 2018 / Online: 12 November 2018 (09:58:50 CET)

A peer-reviewed article of this Preprint also exists.

Ruzzolini, J.; Peppicelli, S.; Andreucci, E.; Bianchini, F.; Scardigli, A.; Romani, A.; la Marca, G.; Nediani, C.; Calorini, L. Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies. Nutrients 2018, 10, 1950. Ruzzolini, J.; Peppicelli, S.; Andreucci, E.; Bianchini, F.; Scardigli, A.; Romani, A.; la Marca, G.; Nediani, C.; Calorini, L. Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies. Nutrients 2018, 10, 1950.

Journal reference: Nutrients 2018, 10, 1950
DOI: 10.3390/nu10121950

Abstract

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained the interest of many scientists thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate cytotoxicity of conventional drugs used to treat melanoma, disclosing new potential therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 μM, to stimulate apoptosis in melanoma cells, while at a non-toxic dose of 250 μM, it affected cell proliferation and induced the downregulation of pAKT/pS6 pathway. 250 μM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increase the cytotoxic effect of Dacarbazine (DTIC). The mayor effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, possibly cooperating in the inhibition of pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and, particularly, RAD001 efficacy on BRAF melanoma cells than Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting pAKT/pS6 pathway.

Subject Areas

BRAF melanoma; chemotherapeutics; extra virgin oil; Oleuropein; olive leaf extract

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