The Major Cyclic Trimeric Product of Indole-3-carbinol Is a Strong Agonist of the Estrogen Receptor Signaling Pathway† Export

@article{citeulike:5249979, abstract = {PMID: 10653634 Indole-3-carbinol (I3C), a component of Brassica vegetables, is under study as a preventive agent of cancers of the breast and other organs. Following ingestion, I3C is converted to a series of oligomeric products that presumably are responsible for the in vivo effects of I3C. We report the effects of the major trimeric product, 5,6,11,12,17,18-hexahydrocyclonona[1,2-b:4,5-b`:7,8-b` `]triindole (CTr), on the estrogen receptor (ER) signaling pathways. Tumor-promoting effects of high doses of I3C may be due to activation of aryl hydrocarbon receptor (AhR)-mediated pathways; therefore, we also examined the effects of CTr on AhR activated processes. We observed that CTr is a strong agonist of ER function. CTr stimulated the proliferation of estrogen-responsive MCF-7 cells to a level similar to that produced by estradiol (E2) but did not affect the growth of the estrogen-independent cell line, MDA-MD-231. CTr displaced E2 in competitive-binding studies and activated ER-binding to an estrogen responsive DNA element in gel mobility shift assays with EC50s of about 0.1 muM. CTr activated transcription of an E2-responsive endogenous gene and exogenous reporter genes in transfected MCF-7 cells, also with high potency. CTr failed to activate AhR-mediated pathways, consistent with the low-binding affinity of CTr for the AhR reported previously. Comparisons of the conformational characteristics of CTr with other ER ligands indicated a remarkable similarity with tamoxifen, a selective ER antagonist used as a breast cancer therapeutic agent and suggest an excellent fit of CTr into the ligand-binding site of the ER.}, author = {Riby, Jacques E. and Feng, Chunling and Chang, Yu-Chen and Schaldach, Charlene M. and Firestone, Gary L. and Bjeldanes, Leonard F.}, citeulike-article-id = {5249979}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi9919706}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi9919706}, day = {1}, doi = {10.1021/bi9919706}, journal = {Biochemistry}, keywords = {dim, indole}, month = {February}, number = {5}, pages = {910--918}, posted-at = {2009-07-24 12:13:49}, priority = {2}, title = {The Major Cyclic Trimeric Product of Indole-3-carbinol Is a Strong Agonist of the Estrogen Receptor Signaling Pathway{\dag}}, url = {http://dx.doi.org/10.1021/bi9919706}, volume = {39}, year = {2000} }

TY - JOUR ID - citeulike:5249979 L3 - citeulike-article-id:5249979 N2 - PMID: 10653634 Indole-3-carbinol (I3C), a component of Brassica vegetables, is under study as a preventive agent of cancers of the breast and other organs. Following ingestion, I3C is converted to a series of oligomeric products that presumably are responsible for the in vivo effects of I3C. We report the effects of the major trimeric product, 5,6,11,12,17,18-hexahydrocyclonona[1,2-b:4,5-b`:7,8-b` `]triindole (CTr), on the estrogen receptor (ER) signaling pathways. Tumor-promoting effects of high doses of I3C may be due to activation of aryl hydrocarbon receptor (AhR)-mediated pathways; therefore, we also examined the effects of CTr on AhR activated processes. We observed that CTr is a strong agonist of ER function. CTr stimulated the proliferation of estrogen-responsive MCF-7 cells to a level similar to that produced by estradiol (E2) but did not affect the growth of the estrogen-independent cell line, MDA-MD-231. CTr displaced E2 in competitive-binding studies and activated ER-binding to an estrogen responsive DNA element in gel mobility shift assays with EC50s of about 0.1 muM. CTr activated transcription of an E2-responsive endogenous gene and exogenous reporter genes in transfected MCF-7 cells, also with high potency. CTr failed to activate AhR-mediated pathways, consistent with the low-binding affinity of CTr for the AhR reported previously. Comparisons of the conformational characteristics of CTr with other ER ligands indicated a remarkable similarity with tamoxifen, a selective ER antagonist used as a breast cancer therapeutic agent and suggest an excellent fit of CTr into the ligand-binding site of the ER. IS - 5 JF - Biochemistry EP - 918 TI - The Major Cyclic Trimeric Product of Indole-3-carbinol Is a Strong Agonist of the Estrogen Receptor Signaling Pathway† VL - 39 SP - 910 KW - dim KW - indole AU - Riby, Jacques AU - Feng, Chunling AU - Chang, Yu-Chen AU - Schaldach, Charlene AU - Firestone, Gary AU - Bjeldanes, Leonard PY - 2000/02/01/ UR - http://dx.doi.org/10.1021/bi9919706 ER -