A ferutinin analogue with enhanced potency and selectivity against ER-positive breast cancer cells in vitro

• Published in: Biomedicine & pharmacotherapy Vol. 105; pp. 267 - 273
• Main Authors: Safi, Rémi, Hamade, Aline, Bteich, Najat, El Saghir, Jamal, Assaf, Mona Diab, El-Sabban, Marwan, Najjar, Fadia
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2018
• Subjects: Breast cancer; Estrogen; Ferutinin; Hemi-synthetic analogue; Stem/progenitor cells; BC; Hemi-synthetic analogue; BCSCs; Estrogen; FRT; HRT; E2; SC; SD; Ferutinin; FBS; Stem/progenitor cells; IC50; p-ER; CSCs; SFU; Breast cancer; SERM; EDTA; ER; 3D; Ca2; HAEC; PI; CTL
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.05.058

[Display omitted] •A hemi-synthetic analogue of the natural phytoestrogen ferutinin is designed to overcome its estrogenic activity.•Ferutinin analogue induces a cytotoxic effect 30 times higher than that of ferutinin towards MCF-7 cell line.•Treatment with ferutinin analogue (1 μM) produced significant accumulation of cells at the pre G0/G1 cell cycle phase.•Ferutinin analogue inhibit the proliferation of MCF-7 cell line and consistently target their stem cells. Estrogen is considered a risk factor for breast cancer since it promotes breast-cell proliferation. The jaesckeanadiol-3-p-hydroxyphenylpropanoate, a hemi-synthetic analogue of the natural phytoestrogen ferutinin (jaesckeanadiol-p-hydroxybenzoate), is designed to be devoid of estrogenic activity. This analogue induces a cytotoxic effect 30 times higher than that of ferutinin towards MCF-7 breast cancer cell line. We compared these two compounds with respect to their effect on proliferation, cell cycle distribution and cancer stem-like cells in the MCF-7 cell line. Treatment with ferutinin (30 μM) and its analogue (1 μM) produced significant accumulation of cells at the pre G0/G1 cell cycle phase and triggered apoptosis. Importantly, this compound retains its anti-proliferative activity against breast cancer stem/progenitor cells that are naturally insensitive to ferutinin at the same dose. These results position ferutinin analogue as an effective compound inhibiting the proliferation of estrogen-dependent breast cancer cells and consistently targeting their stem-like cells.