Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines.
Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.
Nakagawa
H
H
Department of Surgery II, Kansai Medical University, Moriguchi, Osaka, Japan.
Yamamoto
D
D
Kiyozuka
Y
Y
Tsuta
K
K
Uemura
Y
Y
Hioki
K
K
Tsutsui
Y
Y
Tsubura
A
A
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D002453:Cell Cycle / Q000187:drug effects*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D007312:Eulipotyphla; D005260:Female; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D011960:Receptors, Estrogen; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D015118:Eicosapentaenoic Acid; D019833:Genistein