A ferutinin analogue with enhanced potency and selectivity against ER-positive breast cancer cells in vitro
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Elsevier Masson SAS
Abstract
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. © 2018 Elsevier Masson SAS
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Breast cancer, Estrogen, Ferutinin, Hemi-synthetic analogue, Stem/progenitor cells, Apoptosis, Benzoates, Breast neoplasms, Bridged bicyclo compounds, Cell cycle, Cell proliferation, Cell self renewal, Cell survival, Cycloheptanes, Female, Humans, Mcf-7 cells, Neoplastic stem cells, Receptors, estrogen, Sesquiterpenes, Spheroids, cellular, Antineoplastic agent, Jaesckeanadiol 3 (4 hydroxyphenylpropanoate), Phytoestrogen, Unclassified drug, 4-oxy-6-(4-oxybezoyloxy)dauc-8,9-en, Benzoic acid, Cycloheptane derivative, Estrogen receptor, Sesquiterpene, Antineoplastic activity, Antiproliferative activity, Article, Cancer cell, Cancer stem cell, Cell viability, Comparative effectiveness, Controlled study, Drug potency, Drug selectivity, Estrogen receptor positive breast cancer, G1 phase cell cycle checkpoint, Human, Human cell, In vitro study, Mcf-7 cell line, Priority journal, Stem cell self-renewal, Breast tumor, Cell self-renewal, Chemistry, Drug effect, Metabolism, Multicellular spheroid, Pathology