Endocrine Disrupting Activities of the Flavonoid Nutraceuticals Luteolin and Quercetin
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Dietary plant flavonoids have been proposed to contribute to cancer prevention, neuroprotection, and cardiovascular health through their anti-oxidant, anti-inflammatory, pro-apoptotic, and antiproliferative activities. As a consequence, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks. We show that two flavonoids, luteolin and quercetin, are promiscuous endocrine disruptors. These flavonoids display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model. Concurrently, luteolin possesses potent estrogen agonist activity while quercetin is considerably less effective. These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy, plant-rich diet.
KeywordsFlavonoid Quercetin Progesterone Receptor Chronic Fatigue Syndrome Antagonist Activity
The authors thank S. Axlund for the T47D cell line containing a stably integrated CK5-luciferase reporter and for her help with the immunofluorescence experiments. M. Scully provided the Ishikawa cell line expressing estrogen receptor. We thank L. Litzenberger and S. Axlund for their assistance in the preparation of figures and K. Connaghan for guiding the statistical analysis. T.A.J. is supported by NIH/NCI R01CA125427and S.K.N by a dean’s bridge grant. University of Colorado Cancer Center Flow Cytometry and Cell Culture Shared Resources were supported by Cancer Center Support Grant (P30CA046934).
Conflict of Interest
The authors declare that they have no conflict of interest.
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