The cells used in this study MDA-MB-435, are breast cancer cells and unfortunately resveratrol has a bit of a schizophrenic attitude to the many different types of BC cells.
Resveratrol is a phytoestrogen and appears to have a dual effect on estrogen receptors when faced with different types of BC cells. It can antagonise estrogen in some receptors when faced with one type of BC cell and increase estrogen when faced with a different type of BC cell.
This could account for it protecting against some types of cancer cells and on the other hand, allowing an increase in BC cells in other types of BC cancer cells.
In this respect it acts rather like like the drug tamoxifen which is effective against BC but can cause an increase in cancer of the uterus.
Resveratrol produced greater maximal transcriptional activation than estradiol, but this superagonism was not seen in all cell types. For example, resveratrol produced two to four times greater activation of reporter plasmids than estradiol in MCF-7 breast cancer cells but less activation than estradiol in BG-1 ovarian carcinoma cells. These cell type-specific effects of resveratrol are reminiscent of the well known tissue-specific and species-specific effects of agents such as tamoxifen (27), which can act as an estrogen receptor agonist in some tissues such as the uterus but acts as an estrogen antagonist in the breast (27). Other recently characterized estrogen receptor ligands such as raloxifene also appear to exert tissue-selective actions (28).
Estrogenic and Anti-estrogenic Activities
estrogens are steroid
by humans and other mammals; these hormones bind to estrogen receptors within cells. The estrogen-receptor complex interacts with unique sequences in DNA (estrogen response elements; EREs) to modulate the expression
of estrogen-responsive genes (17)
. A compound that binds to estrogen receptors and elicits similar responses to endogenous estrogens is considered an estrogen agonist, while a compound that binds estrogen receptors but prevents or inhibits the response elicited by endogenous estrogens is considered an estrogen antagonist. The chemical structure of resveratrol is very similar to that of the synthetic estrogen agonist, diethylstilbestrol (see figure 2
), suggesting that resveratrol might also function as an estrogen agonist. However, in cell culture experiments resveratrol acts as an estrogen agonist under some conditions and an estrogen antagonist under other conditions (18, 19). In estrogen receptor-positive breast cancer cells, resveratrol acted as an estrogen agonist in the absence of the endogenous estrogen, 17beta-estradiol, but acted as an estrogen antagonist in the presence of 17beta-estradiol (20, 21). At present, it appears that resveratrol has the potential to act as an estrogen agonist or antagonist depending on such factors as cell type, estrogen receptor isoform (ER alpha or ER beta), and the presence of endogenous estrogens (17).
Retailers of resveratrol normally point out that women who have breast cancer or who have had it should not take resveratrol.