Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

Journal Article · Sat Jun 01 04:00:00 EDT 2013 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2013.03.014· OSTI ID:22285304

Rijk, Jeroen C.W. ^[1]; Nijmeijer, Sandra M.; Berg, Martin van den ^[2]

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1. RIKILT - Institute for Food Safety, Wageningen UR, P.O. Box 230, 6700 AE, Wageningen (Netherlands)
2. Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands)

Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast cancer model. • Letrozole or tamoxifen treatment is used to inhibit ER-dependent breast tumor growth. • Phytoestrogens induce in vitro tumor cell growth, even in combination with LET or TAM. • Use of phytoestrogens during breast cancer treatment should better be avoided.

• OSTI ID: 22285304
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 269; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
ESTROGENS
IN VITRO
MAMMARY GLANDS
NEOPLASMS
RECEPTORS
TAMOXIFEN
TUMOR CELLS
WOMEN