Structure-activity relationships of resveratrol and derivatives in breast cancer cells.
Article Details
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Lappano R, Rosano C, Madeo A, Albanito L, Plastina P, Gabriele B, Forti L, Stivala LA, Iacopetta D, Dolce V, Ando S, Pezzi V, Maggiolini M
Structure-activity relationships of resveratrol and derivatives in breast cancer cells.
Mol Nutr Food Res. 2009 Jul;53(7):845-58. doi: 10.1002/mnfr.200800331.
- PubMed ID
- 19496085 [ View in PubMed]
- Abstract
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 ERalpha-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 ERalpha: 3,4'-DHS > 4,4'-DHS > 4-HS > RSV, while 3,5-DHS did not elicit any ligand properties. Computational docking analysis and real-time PCR revealed for each analog a distinct ERalpha 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 ERalpha-mediated biological responses observed in estrogen-sensitive cancer cells.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Resveratrol Estrogen receptor alpha Protein Humans UnknownNot Available Details - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Estradiol Approved Investigational Vet Approved CCNA2 890 upregulated Estradiol results in increased expression of CCNA2 mRNA 4q27 Estradiol Approved Investigational Vet Approved CCND1 595 upregulated Estradiol metabolite results in increased expression of CCND1 mRNA 11q13.3 Estradiol Approved Investigational Vet Approved CTSD 1509 upregulated Estradiol results in increased expression of CTSD mRNA 11p15.5 Estradiol Approved Investigational Vet Approved FOS 2353 upregulated Estradiol results in increased expression of FOS mRNA 14q24.3 Estradiol Approved Investigational Vet Approved PGR 5241 upregulated Estradiol results in increased expression of PGR mRNA 11q22.1 Estradiol Approved Investigational Vet Approved TFF1 7031 upregulated Estradiol results in increased expression of TFF1 mRNA 21q22.3 Resveratrol Investigational CCNA2 890 upregulated resveratrol metabolite results in increased expression of CCNA2 mRNA 4q27 Resveratrol Investigational CCND1 595 upregulated resveratrol metabolite results in increased expression of CCND1 mRNA 11q13.3 Resveratrol Investigational CTSD 1509 upregulated resveratrol metabolite results in increased expression of CTSD mRNA 11p15.5 Resveratrol Investigational FOS 2353 upregulated resveratrol metabolite results in increased expression of FOS mRNA 14q24.3 Resveratrol Investigational PGR 5241 upregulated resveratrol metabolite results in increased expression of PGR mRNA 11q22.1 Resveratrol Investigational TFF1 7031 upregulated resveratrol metabolite results in increased expression of TFF1 mRNA 21q22.3