Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice.

Abstract	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.
Authors	Young H Ju, Daniel R Doerge, Kimberly F Allred, Clinton D Allred, William G Helferich
Journal	Cancer research (Cancer Res) Vol. 62 Issue 9 Pg. 2474-7 (May 01 2002) ISSN: 0008-5472 [Print] United States
PMID	11980635 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Receptors, Progesterone Tamoxifen Cyclin D1 afimoxifene Estradiol Genistein
Topics	Animals Antineoplastic Combined Chemotherapy Protocols (pharmacology) Breast Neoplasms (blood, drug therapy, pathology) Cell Division (drug effects) Cyclin D1 (biosynthesis) Diet Drug Interactions Estradiol (blood, pharmacology) Female Genistein (blood, pharmacology) Humans Mice Mice, Inbred BALB C Mice, Nude Neoplasms, Hormone-Dependent (drug therapy, pathology) Receptors, Progesterone (biosynthesis) Tamoxifen (analogs & derivatives, antagonists & inhibitors, blood, pharmacology) Xenograft Model Antitumor Assays

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