New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo.
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.
['Samara|Pinelopi|P|', 'Christoforidou|Nikoleta|N|', 'Lemus|Christelle|C|', 'Argyropoulou|Aikaterini|A|', 'Ioannou|Kyriaki|K|', 'Vougogiannopoulou|Konstantina|K|', 'Aligiannis|Nektarios|N|', 'Paronis|Efthimios|E|', 'Gaboriaud-Kolar|Nicolas|N|', 'Tsitsilonis|Ourania|O|', 'Skaltsounis|Alexios-Leandros|AL|']
D000818:Animals D000970:Antineoplastic Agents D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D006801:Humans D057888:Iridoid Glucosides D039823:Iridoids D008297:Male D008546:Melanoma, Experimental D051379:Mice D008810:Mice, Inbred C57BL D015394:Molecular Structure D013329:Structure-Activity Relationship D014407:Tumor Cells, Cultured
Oleuropein In vivo Semi-synthesis Cytotoxicity screening Innate immune system Melanoma Olea europaea