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

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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

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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	Unknown	Not 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