Extra Virgin Olive Oil Secoiridoids Modulate the Metabolic Activity of Dacarbazine Pre-Treated and Treatment-Naive Melanoma Cells

Abstract

Nowadays, many individuals, whether healthy or diagnosed with disease, tend to expose themselves to various easily accessible natural products in hopes of benefiting their health and well-being. Mediterranean populations have traditionally used olive oil not only in nutrition but also in cosmetics, including skincare. In this study, the phenolic profile—composed of twelve compounds altogether, including the secoiridoids oleocanthal (OCAL) and oleacein (OCEIN)—of extra virgin olive oil (EVOO) from autochthonous cultivars from Croatia was determined using 1H qNMR spectroscopy and HPLC-DAD analysis, and its biological activity was investigated in melanoma cell lines. The EVOO with the highest OCEIN content had the strongest anti-cancer activity in A375 melanoma cells and the least toxic effect on the non-cancerous keratocyte cell line (HaCaT). On the other hand, pure OCAL was shown to be more effective and safer than pure OCEIN. Post-treatment with any of the EVOO phenolic extracts (EVOO-PEs) enhanced the anti-cancer effect of the anti-cancerous drug dacarbazine (DTIC) applied in pre-treatment, while they did not compromise the viability of non-cancerous cells. The metastatic melanoma A375M cell line was almost unresponsive to the EVOO-PEs themselves, as well as to pure OCEIN and OCAL. Our results demonstrate that olive oils and/or their compounds may have a potentially beneficial effect on melanoma treatment. However, their usage can be detrimental or futile, especially in healthy cells, due to inadequately applied concentrations/combinations or the presence of resistant cells.

Oleocanthal, an Antioxidant Phenolic Compound in Extra Virgin Olive Oil (EVOO): A Comprehensive Systematic Review of Its Potential in Inflammation and Cancer

“…This long-term moderation of inflammation may ultimately lead to substantial decreases in the risk of developing chronic inflammatory conditions, including cancer. In contrast with other polyphenols such as oleacein, OC demonstrated superior effectiveness and safety [44].…”

“…In cutaneous malignant melanoma, although little information is available, Fogli et al demonstrated that OC was able to inhibit ERK1/2 and AKT phosphorylation and downregulate Bcl-2 expression [43]. In contrast with other polyphenols like oleacein, OC proved to be more efficient and safer as a melanoma treatment [44]. The efficacy of OC in non-melanoma cancer cells was also evaluated; Polini et al revealed that oleocanthal and oleacein exhibited noteworthy pharmacological effects by proficiently impeding Erk and Akt phosphorylation, concurrently repressing B-Raf expression [45].…”

Influence of Drying Temperature and Harvesting Season on Phenolic Content and Antioxidant and Antiproliferative Activities of Olive (Olea europaea) Leaf Extracts

“…In this sense, olive leaf extracts have demonstrated activity against almost all of the most common cancers, including breast [10], hepatic [11] and colorectal cancer [12]. In addition, numerous studies have reported the antitumoral effects of other raw materials, such as oils and agri-food byproducts obtained from olive [13][14][15][16][17]. Pure compounds obtained from olives, olive products and olive-related industries have also been extensively studied [18][19][20][21].…”