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Nutrients 2018, 10(12), 1950; https://doi.org/10.3390/nu10121950

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

1
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
2
PHYTOLAB (Pharmaceutical, Cosmetic, Food Supplement Technology and Analysis)-DiSIA, Scientific and Technological Pole, University of Florence, 50134 Florence, Italy
3
Mass Spectrometry Laboratory, Clinic of Pediatric Neurology, Meyer University Children’s Hospital, 50139 Florence, Italy
4
Istituto Toscano Tumori and Center of Excellence for Research, Transfer and High Education DenoTHE University of Florence, 50139 Florence, Italy
*
Authors to whom correspondence should be addressed.
Received: 9 November 2018 / Revised: 30 November 2018 / Accepted: 5 December 2018 / Published: 8 December 2018
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Abstract

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained scientific interest thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate the cytotoxicity of conventional drugs used to treat melanoma, disclosing a potentially new 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, while at a non-toxic dose of 250 µM, it affected cell proliferation and induced the downregulation of the pAKT/pS6 pathway. A dose of 250 µM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increasing the cytotoxic effect of Dacarbazine (DTIC). The major effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, which possibly cooperate in the inhibition of the pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and RAD001 efficacy on BRAF melanoma cells with respect to Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting the pAKT/pS6 pathway. View Full-Text
Keywords: BRAF melanoma; chemotherapeutics; extra virgin oil; Oleuropein; olive leaf extract BRAF melanoma; chemotherapeutics; extra virgin oil; Oleuropein; olive leaf extract
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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.

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