Abstract
The potential “health benefits” of dietary polyphenols have been ascribed to their direct antioxidant activity and their impact on the regulation of cell and tissue redox balance. However, because of the relative poor bioavailability of many of these compounds, their effects could not be easily explained by the antioxidant action, which may occur only at high circulating and tissue concentrations. Therefore, many efforts have been put forward to clarify the molecular mechanisms underlining the biological effect of polyphenols in physiological and pathological conditions. Polyphenols’ bioavailability, metabolism, and their effects on enzyme, membrane, and/or nuclear receptors and intracellular transduction mechanisms may define the overall impact of these compounds on cancer risk and progression, which is still debated and not yet clarified. Polyphenols are able to bind to estrogen receptor α (ERα) and β (ERβ), and therefore induce biological effects in human cells through mimicking or inhibiting the action of endogenous estrogens, even at low concentrations. In this work, the role and effects of food-contained polyphenols in hormone-related cancers will be reviewed, mainly focusing on the different polyphenols’ mechanisms of action with particular attention on their estrogen receptor-based effects, and on the consequences of such processes on tumor progression and development.
Highlights
Polyphenols constitute one of the most numerous and widely distributed groups of natural products in the plant kingdom
The high number of different polyphenols that are found in food, as well as in mixture, and the extensive metabolism that polyphenols undergo in human gut and liver as well as the several, and somewhat contradictory, action mechanisms reported have been the major difficulties in elucidating the effects of dietary polyphenols on cancer [3]
Given the distinct pro- and anti-cancerous effects mediated by estrogen receptor α (ERα) and ERβ, respectively, the balance of ERα and ERβ expression together with the specific function of polyphenols on the different subtypes represent the main factor that defines the effects of such compounds on cancer progression. We identified that both naringenin and quercetin impair, even in the presence of E2, the ERα-activated rapid signaling that is important for the cyclin D1 expression, and for cell cycle progression, without affecting the transcriptional effect of activated ERα [52,114]
Summary
Polyphenols constitute one of the most numerous and widely distributed groups of natural products in the plant kingdom. The phenolic ring that characterizes these compounds allows them to bind to estrogen receptor subtypes (i.e., ERα and ERβ) [7,8], inducing estrogenic or antiestrogenic responses in the target cells by blocking or altering the effects of the endogenous hormone (i.e., 17β-estradiol, E2). This evidence led to the insertion of dietary polyphenols in the class of selective ER modulators [9,10], rendering necessary the re-evaluation of the effect of polyphenols on cancer cells. The overview of polyphenols’ chemical structure, sources, and effect on cancer disease will be reviewed, with a particular attention to the effects of polyphenols as ER modulators and the consequences of such function on tumor progression and development
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