The Effect of the Phytoestrogens Genistein, Daidzein, and Equol on the Growth of Tamoxifen-Resistant T47D/PKCα

@article{Tonetti2007TheEO,
  title={The Effect of the Phytoestrogens Genistein, Daidzein, and Equol on the Growth of Tamoxifen-Resistant T47D/PKC$\alpha$},
  author={Debra A Tonetti and Yiyun Zhang and Huiping Zhao and Sok Bee Lim and Andreas Constantinou},
  journal={Nutrition and Cancer},
  year={2007},
  volume={58},
  pages={222 - 229}
}
Abstract Soy supplements are often consumed by women for alleviating menopausal symptoms or for the perceived protective effects against breast cancer. More concerning is the concurrent consumption of soy isoflavones with tamoxifen (TAM) for prevention or treatment of breast cancer. We previously described a T47D:A18/protein kinase C (PKC)α TAM-resistant tumor model that exhibits autonomous growth and estradiol-induced tumor regression. We compared the estrogenicity of the isoflavones genistein… 
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TLDR
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OF PHARMACOLOGICAL EFFECTS
TLDR
Daidzein appears to play a significant role in the prevention of a variety of diseases and has the potential of being used in a clinical setting, however, further research is needed to understand its molecular mechanisms and safety for use in humans.
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References

SHOWING 1-10 OF 46 REFERENCES
Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice.
TLDR
Daidzein and (+/-)-equol have proliferative effects on MCF-7 cell growth in vitro within the concentration range tested and suggest that pharmacokinetic and/or metabolic factors attenuate the estrogenic effects of daidzesin and equol in vivo.
Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner.
TLDR
It is hypothesize that soy isolates containing different concentrations of genistein will stimulate the growth of estrogen-dependent cells in vivo in a dose-dependent manner and test this hypothesis by feeding soy protein isolates to athymic mice implanted with estrogen- dependent tumors.
Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells.
Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.
TLDR
Dietary genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression.
The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours.
Chemopreventive Effects of Soy Protein and Purified Soy Isoflavones on DMBA-Induced Mammary Tumors in Female Sprague-Dawley Rats
TLDR
Results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.
Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate.
TLDR
Dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways and down-regulated androgen receptor, estrogen receptor-alpha, progesterone receptor, epidermal growth factor receptor, insulin-like growth factor-I, and extracellular signal-regulated kinase-1.
Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice.
TLDR
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).
Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice.
TLDR
Dietary treatment withgenistein at physiological concentrations produces blood levels of genistein sufficient to stimulate estrogenic effects, such as breast tumor growth, cellular proliferation and pS2 expression in athymic mice in a dose-responsive manner similar to that seen in vitro.
Differential response to phytoestrogens in endocrine sensitive and resistant breast cancer cells in vitro
TLDR
In vitro data suggests that phytoestrogens could have potentially adverse mitogenic effects on tumour cells and should probably be avoided by patients who remain sensitive to TAM or in those with pre‐existing and possibly undiagnosed breast tumours.
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