Potent inhibition of breast cancer cell lines by the isoflavonoid kievitone: comparison with genistein.
The isoflavonoid kievitone potently inhibited the proliferation of the oestrogen receptor (ER)-positive breast cancer cell lines MCF-7 and T47D and the ER-negative breast cancer cell line SKBR3 (IC50 values 5-18 microM). DNA synthesis of MCF-7 cells stimulated by insulin-like growth factor 1, insulin-like growth factor 2, basic fibroblast growth factor or transforming growth factor alpha was inhibited by similar concentrations of kievitone (IC50 values 1-3 microM). DNA synthesis stimulated by 17, beta-oestradiol was also inhibited (IC50 = 6 microM). Compared with kievitone, genistein was 3-9 fold weaker as an inhibitor of the proliferation of the breast cancer cell lines and of growth factor-stimulated DNA synthesis. However, genistein was about 5-fold more potent than kievitone as an inhibitor of solubilised epidermal growth factor (EGF) receptor kinase activity and EGF receptor autophosphorylation.
Hoffman
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Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge, UK.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D007887:Fabaceae; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D010766:Phosphorylation; D010946:Plants, Medicinal; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000094162:Phytoalexins
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D016222:Fibroblast Growth Factor 2; D019833:Genistein; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D007529:Isoflavones; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C094208:kievitone; D000094162:Phytoalexins