Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice.
The use of dietary isoflavone supplements by postmenopausal women with breast cancer is increasing. We investigated interactions between the soy isoflavone, genistein, and an antiestrogen, tamoxifen (TAM), on the growth of estrogen (E)-dependent breast cancer (MCF-7) cells implanted in ovariectomized athymic mice. We hypothesized that weakly estrogenic genistein negate/overwhelm the inhibitory effect of TAM on the growth of E-dependent breast tumors. Six treatment groups were used: control (C); 0.25 mg estradiol (E2) implant (E); E2 implant + 2.5 mg TAM implant (2.5 TE); E2 implant + 2.5 mg TAM implant + 1000 ppm genistein (2.5 TEG); E2 implant + 5 mg TAM implant (5 TE), and E2 implant +5 mg TAM implant +1000 ppm genistein (5 TEG). Treatment with TAM (2.5 TE and 5 TE) suppressed E2-stimulated MCF-7 tumor growth in ovariectomized athymic mice. Dietary genistein negated/overwhelmed the inhibitory effect of TAM on MCF-7 tumor growth, lowered E2 level in plasma, and increased expression of E-responsive genes (e.g., pS2, PR, and cyclin D1). Therefore, caution is warranted for postmenopausal women consuming dietary genistein while on TAM therapy for E-responsive breast cancer.
Ju
Young H
YH
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Doerge
Daniel R
DR
Allred
Kimberly F
KF
Allred
Clinton D
CD
Helferich
William G
WG
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D004032:Diet; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D011980:Receptors, Progesterone; D013629:Tamoxifen; D019938:Cyclin D1; C016601:afimoxifene; D004958:Estradiol; D019833:Genistein