Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice
Open accessAbstract
The objective of this work was to determine the interactive effects between soy bioactive components and tamoxifen (TAM) on prevention of estrogen-dependent breast cancer (BRCA). We initially investigated the effects of soy isoflavone genistein and TAM on the growth and cell cycle progression of estrogen-dependent MCF-7 human BRCA cells, and on the expression of ERalpha, pS2 and EGFR genes in vitro. Genistein or TAM alone inhibited the growth of MCF-7 cells in part via G(1) phase arrest, but their combinations showed suggestive antagonistic effects. We further evaluated the effects of bioactive soy components and TAM on the growth inhibition of MCF-7 tumors in a clinically relevant breast tumor model. TAM and bioactive soy components, genistein and soy phytochemical concentrate (SPC), delayed the growth of MCF-7 tumors. The combination of TAM with genistein or SPC, especially at the lower dose of TAM, had synergistic effects on delaying the growth of MCF-7 tumors. Biomarker determination suggests that the combination of TAM and soy components may synergistically delay the growth of MCF-7 tumors via their combined effects on induction of tumor cell apoptosis and inhibition of tumor cell proliferation. In addition, genistein and TAM combination synergistically delayed the growth of breast tumor via decreased estrogen level and activity, and down-regulation of EGFR expression. The results from our studies suggest that further investigations may be warranted to determine if the combination of TAM and bioactive soy components may be used for prevention and/or treatment of estrogen-dependent BRCA.
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Some preliminary evidence indicates that isoflavones may have synergistic effects with tamoxifen in cancer models and may reduce the development of tamoxifen resistance.
“Some preliminary evidence indicates that isoflavones may have synergistic effects with tamoxifen in cancer models and may reduce the development of tamoxifen resistance [185,186].”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [186]
The Discussion reports additive-to-synergistic inhibition of MCF-7 tumor growth in mice when tamoxifen was combined with genistein or soy phytochemical concentrate. It does not report that isoflavones reduce the development of tamoxifen resistance; the resistance references concern other treatments or studies. (LLM, conf=0.88)
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- Messina,M.J. et al. (1994) Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer, 21, 113-131.
- Messina,M.J. et al. (2001) Soy for breast cancer survivors: a critical review of the literature. J. Nutr., 131, 3095S-3108S.
- Steel,R.G.D. et al. (1980) Principles and Procedures of Statistics: A Bio- metrical Approach. McGraw-Hill book Company, Inc, New York, NY.
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Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review
Fritz, H., Seely, D., Flower, G., Skidmore, B., Fernandes, R., Vadeboncoeur, S., Kennedy, D., Cooley, K., Wong, R., Sagar, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081968 · Cited by 188 · see citing works
- Authors
- Mai, Z., Blackburn, G. L., & Zhou, J.-R.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Zhou, J.-R.
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-18
- Volume
- 28
- Issue
- 6
- Pages
- 1217-1223
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC2747475
- OpenAlex
- W2165455321
- Cited by
- 64
- References
- 0
- Citations by year
- 2025: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2015: 3 · 2014: 5 · 2013: 11 · 2012: 7
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Breast Cancer Research Foundation
- U.S. Public Health Service
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK040561)
- National Center for Complementary and Integrative Health (R01AT000863)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- tamoxifen, genistein, estrogen-dependent breast cancer, MCF-7 cells, synergistic drug combination, breast cancer prevention, G1 cell cycle arrest, apoptosis, estrogen receptor alpha, pS2, EGFR, tumor growth inhibition, soy isoflavones
- MeSH terms
- Animals, Breast Neoplasms, Carcinoma, Drug Synergism, Estrogens, Female, Humans, Phytotherapy, Glycine max, Tamoxifen, Mice, SCID, Antineoplastic Agents, Hormonal, Cell Line, Tumor, Cell Proliferation, Mice
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