Dietary Genistein Negates the Inhibitory Effect of Tamoxifen on Growth of Estrogen-dependent Human Breast Cancer (MCF-7) Cells Implanted in Athymic Mice


Ju YH, Doerge DR, Allred KF, Allred CD, Helferich WG




Cancer Res


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 (E(2)) implant (E); E(2) implant + 2.5 mg TAM implant (2.5 TE); E(2) implant + 2.5 mg TAM implant + 1000 ppm genistein (2.5 TEG); E(2) implant + 5 mg TAM implant (5 TE), and E(2) implant +5 mg TAM implant +1000 ppm genistein (5 TEG). Treatment with TAM (2.5 TE and 5 TE) suppressed E(2)-stimulated MCF-7 tumor growth in ovariectomized athymic mice. Dietary genistein negated/overwhelmed the inhibitory effect of TAM on MCF-7 tumor growth, lowered E(2) 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.