药理学
IC50型
细胞凋亡
癌细胞
MTT法
生物活性
活力测定
细胞生长
癌症研究
作者
Pinelopi Samara,Nikoleta Christoforidou,Christelle Lemus,Aikaterini Argyropoulou,Kyriaki Ioannou,Konstantina Vougogiannopoulou,Nektarios Aligiannis,Efthimios Paronis,Nicolas Gaboriaud-Kolar,Ourania E. Tsitsilonis,Alexios-Leandros Skaltsounis
标识
DOI:10.1016/j.ejmech.2017.05.029
摘要
Oleuropein is a glucosylated seco-iridoid present in olive fruits and leaves. Due to its broad spectrum of biological activities, including anticancer properties, oleuropein has attracted scientific attention for the past 20 years. The promising antiproliferative activity of an olive leaf extract enriched in oleuropein against a series of human cancer cell lines, prompted us to proceed with the semi-synthesis of 51 analogs of oleuropein. Following their initial screening against the estrogen receptor negative breast cancer cell line SKBR3, 7 analogs were shown to display significant cytotoxicity and were further tested against 6 additional solid tumor-derived and leukemic cell lines. The analog with the most promising antitumor activity (24) was selected for more detailed studies. 24 was non-toxic to peripheral blood mononuclear cells derived from healthy blood donors when tested at concentrations close to its half maximal inhibitory concentration. In vivo administration of 24 in melanoma-bearing mice resulted in reducing tumor size in a dose-dependent manner and in inducing anti-melanoma-reactive immune responses. Our results suggest that analog 24, emerging from the initial structure of oleuropein, represents a promising lead structure for further optimization.
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