Flavonoids in food: how potent is their protection?

Telling a child "eat your chemoprotective phytochemicals" is just one way of saying "eat your vegetables--they're good for you!" Now science can back up this parental wisdom with molecular studies that demonstrate plants' disease-fighting potential. In vitro studies have shown that certain phytochemicals called flavonoids interact with the aryl hydrocarbon receptor (AhR), the same receptor through which 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) and other halogenated aromatic compounds exert their toxic and mutagenic effects. In some types of cancer cells, flavonoids may inhibit TCDD from activating the AhR, exerting a chemoprotective effect, report Shu Zhang, Chunhua Qin, and Stephen H. Safe of Texas A&M University [EHP 111:1877-1882].

Zhang and colleagues assert that the traditional method for measuring TCDD toxicity fails to address the increasing evidence that the AhR binds a host of endogenous chemicals considered to be chemoprotective, such as phytochemicals. In other words, TCDD may not be as dangerous to human health as expected, given that we eat foods that may protect against its effects. The team therefore assessed the interaction of TCDD and flavonoids with an eye toward determining whether the effect of flavonoids needs to be taken into consideration when assessing the overall toxicity of TCDD to humans.

The researchers used an AhR-responsive assay to test the action of 13 dietary flavonoids in human breast and liver cancer cells and mouse liver cancer cells. The assay used a luciferase gene that was activated only when the compounds interacted with the AhR in the cell lines.

Some flavonoids turned out to be AhR agonists--that is, they mimicked TCDD's action--and others were antagonists--they blocked stimulation of the AhR by TCDD. Their potency varied, usually by cell type (mouse versus human). The maximum level of agonist activity reached by a flavonoid was just 25% of that reached by TCDD. In terms of antagonist effects, one flavonoid (luteolin) acted as an AhR antagonist, and two (baicalein and cantharidin) triggered production of a protein that helps metabolize carcinogens. "These data suggest that dietary phytochemicals exhibit substantial cell context--dependent AhR agonist as well as antagonist activities," the team reports.

The results of this study complement previous reports showing the AhR agonist and antagonist activities of numerous chemoprotective phytochemicals. Because food has relatively high concentrations of compounds that interact with the AhR, the authors write that "risk assessment of dietary toxic equivalents of TCDD and related compounds should also take into account AhR agonist/antagonist activities of phytochemicals."