PLANT-DERIVED FLAVONOID NUTRACEUTICALS ARE MULTI-FUNCTIONAL ENDOCRINE DISRUPTORS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 366-382-Physiological Impacts of Endocrine Disrupting Chemicals
Basic/Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-382
Steven K Nordeen*, Betty J. Bona, David N. Jones and Twila A Jackson
Univ Colorado School of Medicine, Aurora, CO
Diets rich in fruits and vegetables are associated with lower incidence of disease including cancer and cardiovascular disease.  Flavonoids are major components of plant-rich diets and have anti-oxidant, anti-inflammatory, and anti-proliferative activities that may contribute to a reduced risk of cancer, the benefits of a Mediterranean diet, and account for the “French paradox”, the low incidence of cardiovascular mortality despite ingestion of a high fat diets associated with consumption of red wine.  Consequently, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks.  In these studies we show that a series of related flavonoids display a spectrum of endocrine disrupting activities.  Often, the same flavonoid has multiple endocrine disrupting activities.  For example, luteolin has anti-progestin, anti-glucocorticoid, and pro-estrogenic activities on transcriptional targets.  Furthermore, the progesterone antagonist activity of luteolin suppresses the induction of tumor-initiating cells in a breast cancer cell model but inhibits the progestin-mediated block of estrogen-enhanced growth in an endometrial cancer cell model.  Like luteolin, apigenin, a related flavonoid, also has potent pro-estrogenic and progesterone antagonist activity toward transcriptional targets.  Several lines of data are consistent with a competitive mechanism for progestin antagonist action: antagonism can be progressively diminished by increasing doses of agonist, molecular modeling predicts that luteolin and apigenin can occupy the ligand binding site with high affinity, and flavonoids do not decrease levels of progesterone receptor. Notably, the dual estrogen agonist and progesterone antagonist activities of luteolin and apigenin are manifested at levels attainable via dietary consumption.  This suggests that supplementation with these flavonoids be contraindicated for women at risk for endometrial cancer.  These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy plant-rich diet.

Nothing to Disclose: SKN, BJB, DNJ, TAJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Dean's bridging grant to SKN, NIH NCI R01 CA125427 to TAJ.
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