A Systematic Ex-Vivo Study of the Anti-Proliferative/Cytotoxic Bioactivity of Major Olive Secoiridoids' Double Combinations and of Total Olive Oil Phenolic Extracts on Multiple Cell-Culture Based Cancer Models Highlights Synergistic Effects

一项针对多种基于细胞培养的癌症模型,系统性地开展了离体研究,旨在探究主要橄榄环烯醚萜类化合物双重组合及橄榄油总酚提取物的抗增殖/细胞毒性生物活性,并揭示其协同效应。

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作者:Aikaterini Papakonstantinou ,Petrina Koumarianou ,Panagiotis Diamantakos ,Eleni Melliou ,Prokopios Magiatis ,Haralabia Boleti

Abstract

Several individual olive oil phenols (OOPs) and their secoiridoid derivatives have been shown to exert anti-proliferative and pro-apoptotic activity in treatments of human cancer cell lines originating from several tissues. This study evaluated the synergistic anti-proliferative/cytotoxic effects of five olive secoiridoid derivatives (oleocanthal, oleacein, oleuropein aglycone, ligstroside aglycone and oleomissional) in all possible double combinations and of total phenolic extracts (TPEs) on eleven human cancer cell lines representing eight cell-culture-based cancer models. Individual OOPs were used to treat cells for 72 h in half of their EC50 values for each cell line and their synergistic, additive or antagonistic interactions were evaluated by calculating the coefficient for drug interactions (CDI) for each double combination of OOPs. Olive oil TPEs of determined OOPs' content, originating from three different harvests of autochthonous olive cultivars in Greece, were evaluated as an attempt to investigate the efficacy of OOPs to reduce cancer cell numbers as part of olive oil consumption. Most combinations of OOPs showed strong synergistic effect (CDIs < 0.9) in their efficacy, whereas TPEs strongly impaired cancer cell viability, better than most individual OOPs tested herein, including the most resistant cancer cell lines evaluated. Keywords: anti-proliferative efficacy; anticancer properties; cytotoxic efficacy; human cancer cells; oleocanthal; olive oil phenolic extracts; olive phenols combinations; secoiridoid derivatives.

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