In Vitro Anti-Proliferative and Apoptotic Effects of Hydroxytyrosyl Oleate on SH-SY5Y Human Neuroblastoma Cells

Abstract

The antitumor activity of polyphenols derived from extra virgin olive oil and, in particular the biological activity of HTyr, has been studied extensively. However, the use of HTyr as a therapeutic agent for clinical applications is limited by its low bioavailability and rapid excretion in humans. To overcome these limitations, several synthetic strategies have been optimized to prepare lipophenols and new compounds derived from HTyr to increase lipophilicity and bioavailability. One very promising ester is hydroxytyrosyl oleate (HTyr-OL) because the chemical structure of HTyr, which is responsible for several biological activities, is linked to the monounsaturated chain of oleic acid (OA), giving the compound high lipophilicity and thus bioavailability in the cellular environment. In this study, the in vitro cytotoxic, anti-proliferative, and apoptotic induction activities of HTyr-OL were evaluated against SH-SY5Y human neuroblastoma cells, and the effects were compared with those of HTyr and OA. The results showed that the biological activity of HTyr was maintained in HTyr-OL treatments at lower dosages. In addition, the shotgun proteomic approach was used to study HTyr-OL-treated and untreated neuroblastoma cells, revealing that the antioxidant, anti-proliferative and anti-inflammatory activities of HTyr-OL were observed in the unique proteins of the two groups of samples.

Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy

“…HTyr is the main phenol present in EVOO. It is a small, catecholic compound exhibiting antioxidant, cardioprotective, anticancer, neuroprotective and anti-inflammatory activities [ 42 , 43 , 44 , 45 , 46 , 47 ]. Because of these interesting properties, it has a high therapeutic potential and is used as a supplement and preservative for cosmeceutical, nutraceutical and food applications.…”

Olive Polyphenol Oxidase Gene Family

“…The main phenolic components of VOO are the secoiridoid derivatives of hydroxytyrosol (HTy) and tyrosol (Ty), with the hydroxytyrosol-containing phenolic components having the highest biological activities. They are the most effective in preventing chronic diseases due to their superior ability to reduce chronic inflammation and oxidative damage and their potent anti-proliferative activity [ 3 , 4 ]. In this sense, scientific evidence on the health benefits of HTy has led the European Food Safety Authority (EFSA) to approve a health claim that states “olive oil polyphenols contribute to the protection of blood lipids from oxidative stress”.…”

Role of Hydroxytyrosol and Oleuropein in the Prevention of Aging and Related Disorders: Focus on Neurodegeneration, Skeletal Muscle Dysfunction and Gut Microbiota

“…Some authors tested HTyr-rich extracts from olive oil mill wastewater, demonstrating that the extracts exhibit antiproliferative and pro-apoptotic effects on the human HL60 cancer cell line and avoids toxicity in the non-tumor cell line [ 106 ]. A recent study confirmed the induction of apoptotic and antiproliferative activity on SH-SY5Y neuroblastoma cells, comparing the effects with the non-tumoral cell line MCF10A [ 107 ]. The experimental results showed that the highest apoptosis rate was found for HTyr-treated neuroblastoma cells, while the absence of the apoptotic process induction was highlighted for the normal cell line.…”