miRNA Modulation and Antitumor Activity by the Extra-Virgin Olive Oil Polyphenol Oleacein in Human Melanoma Cells

Abstract

Extra-virgin olive oil (EVOO) polyphenols contribute to Mediterranean diet healthpromoting 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.

pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy

“…As shown in Figure 7 , a significant decrease of cell viability was evident with both the IMQ concentrations evaluated (about 15% and 25% of decrease for 20 and 200 ng/mL of IMQ, respectively) when formulated into the nanostructures, but not when tested alone. This latter evidence agrees with previous reports where IMQ on the same cells [ 65 ] and in other cancer cells [ 83 , 84 ] was cytotoxic at concentrations greater than 1 μg/mL. This suggests an improved efficacy of IMQ when formulated in the nanomicellar system.…”

“…Imiquimod is an anticancer agent showing both immune-stimulation activity and a direct cytotoxic/anti-proliferative action [ 65 , 81 , 82 , 83 ]. Therefore, in vitro melanoma cells have been used in the present study as the simplest cancer model to verify the usefulness of the proposed nanostructured system.…”

“…Culture conditions and cell viability assay (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; MTS) were performed in agreement with the ones reported in Carpi et al [ 65 ]. After overnight attachment, cells were incubated with IMQ and C 7 /C 13 CO-HTMG-TPGS-IMQ/Nano at two different concentrations for 24 h. At the end of the treatment, 20 μL of MTS solution was added to each well and absorbance was read at 490 nm using the Infinite M200 NanoQuant instrument (Tecan, Salzburg, Austria).…”

The Extra Virgin Olive Oil Polyphenol Oleocanthal Exerts Antifibrotic Effects in the Liver

“…OC was extracted from EVOO as previously reported ( 18 ), with slight modifications ( 19 ). The purification of OC was performed using advanced automated flash purification (Isolera™Prime 3.2.2, Biotage®) as described for the purification of oleacein ( 20 ). In the first step of purification, Biotage SNAP Ultra cartridge (HP-Sphere TM 25μm) was chosen as stationary phase.…”

Olive Phenomenon from the Mediterranean Diet: Health Promotion via Phytochemicals

“…Oleacein, another abundant secoiridoid in olive and leaves show antitumor activity via controlling the altered pattern of gene expression (transcripts and miRNAs) related to mTOR and BCL2 pathways in melanoma cells. Hydroxytyrosol, the most representative simple phenol of Olea europaea L. leaves and virgin oils, causes inhibition of melanoma cell proliferation activating caspase-3-dependent apoptosis [15,16].…”