Abstract
Extra-virgin olive oil (EVOO) polyphenols contribute to Mediterranean diet health-promoting properties. One of the most abundant secoiridoid present in EVOO, Oleacein (OA), demonstrated anticancer activity against several tumors. Nevertheless, its role against melanoma has not still investigated. This study aimed at determining in vitro the antimelanoma activity of OA and the relative mechanism of action. OA induced cell growth inhibition in 501Mel melanoma cells with an IC50 in the low micromolar range of concentrations. Moreover, an OA concentration approximating the IC50 induced G1/S phase arrest, DNA fragmentation, and downregulation of genes encoding antiapoptotic (BCL2 and MCL1) and proproliferative (c-KIT, K-RAS, PIK3R3, mTOR) proteins, while increased transcription levels of the proapoptotic protein BAX. Concordantly, OA increased the levels of miR-193a-3p (targeting MCL1, c-KIT and K-RAS), miR-193a-5p (targeting PIK3R3 and mTOR), miR-34a-5p (targeting BCL2 and c-KIT) and miR-16-5p (miR-16-5p targeting BCL2, K-RAS and mTOR), while decreased miR-214-3p (targeting BAX). These modulatory effects might contribute to the inhibition of 501Mel melanoma cell growth observed after treatment with an olive leaves-derived formulation rich in OA, with potential application against in situ cutaneous melanoma. Altogether, these results demonstrate the ability of OA to contrast the proliferation of cutaneous melanoma cells through the transcriptional modulation of relevant genes and microRNAs, confirming the anticancer potential of EVOO and suggesting OA as a chemopreventive agent for cancer disease therapy.
Highlights
The epidemiological observation that habitants of Mediterranean countries exhibit longevity and lower incidence of the age-related diseases has been closely linked to their food habits (Capurso et al, 2019)
Compared to other vegetable oils, extra-virgin olive oil (EVOO), in addition to high levels of oleic acid, is characterized by a high amount of phenolic and polyphenolic compounds endowed with antioxidant, antiinflammatory, vasculoprotective actions (Visioli and Bernardini, 2011), which have been reported to be responsible for EVOO main pharmacological and pharma-nutritional properties against the development of several chronic diseases, including cardiovascular diseases, obesity, diabetes, metabolic syndrome, and cancer (Visioli et al, 2018; Crespo et al, 2018)
To investigate the mechanism underlying the inhibition of melanoma cell viability by OA, the analysis of the cell cycle profile of OA-treated cells was investigated by the evaluation of Histone H3-pSer10, a marker of mitosis, and cyclin-dependent kinase 2 (Cdk2)-pTyr15, a marker of the G1/S transition
Summary
The epidemiological observation that habitants of Mediterranean countries exhibit longevity and lower incidence of the age-related diseases has been closely linked to their food habits (Capurso et al, 2019). In this context, the consumption of extra-virgin olive oil (EVOO), obtained from the drupes of the olive tree (Olea Europaea L.), has been clinically associated with the health-promoting properties of the Mediterranean diet (Parkinson and Cicerale, 2016; Lozano-Castellón et al, 2019). Further studies that deepen the role of each polyphenol are needed to better understand their health-promoting contribution
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