Structure-activity relationships of resveratrol and derivatives in breast cancer cells

Resveratrol (RSV) is classified as a phytoestrogen due to its ability to interact with estrogen receptors(ERs). We assessed structure–activity relationships of RSV and the analogs 4,49-dihydroxystilbene(4,49-DHS), 3,5-dihydroxystilbene (3,5-DHS), 3,49-dihydroxystilbene (3,49-DHS), 4-hydroxystilbene(4-HS) using as model systems the ERa-positive and negative MCF7 and SkBr3 breast cancer cells,respectively. In binding assays and transfection experiments RSV and the analogs showed the followingorder of agonism for ERa: 3,49-DHS A 4,49-DHS A 4-HS A RSV, while 3,5-DHS did not elicit anyligand properties. Computational docking analysis and real-time PCR revealed for each analog a distinctERa binding orientation and estrogen target gene expression profile. Interestingly, the aforementionedorder of ligand activity was confirmed in proliferation assays which also showed the lack ofgrowth stimulation by 3,5-DHS. Our data suggest that subtle changes in the structure of the RSVderivatives examined may be responsible for the different ERa-mediated biological responsesobserved in estrogen-sensitive cancer cells.