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 ovariectomize...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-05, Vol.62 (9), p.2474-2477
Main Authors: JU, Young H, DOERGE, Daniel R, ALLRED, Kimberly F, ALLRED, Clinton D, HELFERICH, William G
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Biological and medical sciences
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cell Division - drug effects
Chemotherapy
Cyclin D1 - biosynthesis
Diet
Drug Interactions
Estradiol - blood
Estradiol - pharmacology
Female
Genistein - blood
Genistein - pharmacology
Humans
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Hormone-Dependent - drug therapy
Neoplasms, Hormone-Dependent - pathology
Pharmacology. Drug treatments
Receptors, Progesterone - biosynthesis
Tamoxifen - analogs & derivatives
Tamoxifen - antagonists & inhibitors
Tamoxifen - blood
Tamoxifen - pharmacology
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0008-5472
1538-7445