As we age, there is a natural decrease in estrogen and androgen levels that leads to poor functioning of tissues and organs. This decrease in hormones and hormonal stimulation usually favors cell proliferation instead of cell differentiation and senescence, which can therefore increase the chances of cancer. There is hope however, as hormone dependent tumors such as breast and prostate can be averted by daily consumption of selective estrogen receptor modulators (SERMs).
SERMs are powerful compounds that exert estrogen agonism or antagonism, based on the cell type, expression of genes targeted by estrogen receptors (ERs) and other intracellular responses. Resveratrol is a polyphenol that acts as a phytoestrogen with positive effects on estrogen receptor-expressing and nonexpressing human tumors. RES functions as a phytoestrogen because it has a similar structure to that of synthetic estrogen diethylstilbestrol (4,4′-dihydroxy-trans-diethylstilbene).
RES is a member of the estrogen type I class, meaning it binds to estrogen receptors with weaker affinity than estradiol, acting as a weak competitor. RES also has an antiestrogen effect by generating parallel pathways that block estrogen-induced cellular outcomes, such as proliferation, tumoral transformation and progression. With estrogen present, RES creates a mixed agonistic–antagonistic action in estrogen receptor-positive breast cancer cells. It can therefore be said that RES functions as natural SERM.
The diagram below illustrates how RES can function as a natural SERM.
Pathways in which resveratrol acts as a SERM