TY - JOUR
T1 - Structure-activity relationships of resveratrol and derivatives in breast cancer cells
AU - Lappano, Rosamaria
AU - Rosano, Camillo
AU - Madeo, Antonio
AU - Albanito, Lidia
AU - Plastina, Pierluigi
AU - Gabriele, Bartolo
AU - Forti, Luca
AU - Stivala, Lucia Anna
AU - Iacopetta, Domenico
AU - Dolce, Vincenza
AU - Andò, Sebastiano
AU - Pezzi, Vincenzo
AU - Maggiolini, Marcello
PY - 2009/7
Y1 - 2009/7
N2 - 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 4,4'-dihydroxystilbene (4,4'-DHS), 3,5-dihydroxystilbene (3,5-DHS), 3,4'-dihydroxystilbene (3,4'-DHS), 4-hydroxystilbene (4-HS) using as model systems the ERα-positive and negative MCF7 and SkBr3 breast cancer cells, respectively. In binding assays and transfection experiments RSV and the analogs showed the following order of agonism for ERa: 3,4'-DHS A 4,4'-DHS A 4-HS A RSV, while 3,5-DHS did not elicit any ligand properties. Computational docking analysis and real-time PCR revealed for each analog a distinct ERα binding orientation and estrogen target gene expression profile. Interestingly, the aforementioned order of ligand activity was confirmed in proliferation assays which also showed the lack of growth stimulation by 3,5-DHS. Our data suggest that subtle changes in the structure of the RSV derivatives examined may be responsible for the different ERα-mediated biological responses observed in estrogen-sensitive cancer cells.
AB - 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 4,4'-dihydroxystilbene (4,4'-DHS), 3,5-dihydroxystilbene (3,5-DHS), 3,4'-dihydroxystilbene (3,4'-DHS), 4-hydroxystilbene (4-HS) using as model systems the ERα-positive and negative MCF7 and SkBr3 breast cancer cells, respectively. In binding assays and transfection experiments RSV and the analogs showed the following order of agonism for ERa: 3,4'-DHS A 4,4'-DHS A 4-HS A RSV, while 3,5-DHS did not elicit any ligand properties. Computational docking analysis and real-time PCR revealed for each analog a distinct ERα binding orientation and estrogen target gene expression profile. Interestingly, the aforementioned order of ligand activity was confirmed in proliferation assays which also showed the lack of growth stimulation by 3,5-DHS. Our data suggest that subtle changes in the structure of the RSV derivatives examined may be responsible for the different ERα-mediated biological responses observed in estrogen-sensitive cancer cells.
KW - Breast cancer
KW - Docking analysis
KW - Estrogen receptor
KW - Hydroxystilbenes
KW - Resveratrol
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U2 - 10.1002/mnfr.200800331
DO - 10.1002/mnfr.200800331
M3 - Article
C2 - 19496085
AN - SCOPUS:68149164115
VL - 53
SP - 845
EP - 858
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
SN - 1613-4125
IS - 7
ER -