Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane, a major in vivo product of dietary indole-3-carbinol Export

@article{citeulike:5249972, abstract = {Under acidic conditions, indole-3-carbinol (I3C) is converted to a series of oligomeric products thought to be responsible for the biological effects of dietary I3C. Chromatographic separation of the crude acid mixture of I3C, guided by cell proliferation assay in human MCF-7 cells, resulted in the isolation of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr-1) as a major antiproliferative component. LTr-1 inhibited the growth of both estrogen-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cells by approximately 60\% at a non-lethal concentration of 25 μM. LTr-1 had no apparent effect on the proliferation of MCF-7 cells in the absence of estrogen. LTr-1 was a weak ligand for the estrogen receptor (ER) ( 50 70 μM) and efficiently inhibited the estradiol (E 2 )-induced binding of the ER to its cognate DNA responsive element. The antagonist effects of LTr-1 also were exhibited in assays of endogenous pS2 gene expression and in cells transiently transfected with an estrogen-responsive reporter construct (pERE-vit-CAT). LTr-1 activated both binding of the aryl hydrocarbon (Ah) receptor to its cognate DNA responsive element and expression of the Ah receptor-responsive gene CYP1A1 . LTr-1 was a competitive inhibitor of CYP1A1-dependent ethoxyresorufin- O -deethylase (EROD) activity. In summary, these results demonstrated that LTr-1, a major in vivo product of I3C, could inhibit the proliferation of both estrogen-dependent and -independent breast tumor cells and that LTr-1 is an antagonist of estrogen receptor function and a weak agonist of Ah receptor function.}, author = {Chang, Y.}, citeulike-article-id = {5249972}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/S0006-2952(99)00165-3}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0006-2952(99)00165-3}, day = {1}, doi = {10.1016/S0006-2952(99)00165-3}, issn = {00062952}, journal = {Biochemical Pharmacology}, keywords = {dim, indole}, month = {September}, number = {5}, pages = {825--834}, posted-at = {2009-07-24 12:11:04}, priority = {2}, title = {Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane, a major in vivo product of dietary indole-3-carbinol}, url = {http://dx.doi.org/10.1016/S0006-2952(99)00165-3}, volume = {58}, year = {1999} }

TY - JOUR ID - citeulike:5249972 L3 - citeulike-article-id:5249972 N2 - Under acidic conditions, indole-3-carbinol (I3C) is converted to a series of oligomeric products thought to be responsible for the biological effects of dietary I3C. Chromatographic separation of the crude acid mixture of I3C, guided by cell proliferation assay in human MCF-7 cells, resulted in the isolation of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr-1) as a major antiproliferative component. LTr-1 inhibited the growth of both estrogen-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cells by approximately 60% at a non-lethal concentration of 25 μM. LTr-1 had no apparent effect on the proliferation of MCF-7 cells in the absence of estrogen. LTr-1 was a weak ligand for the estrogen receptor (ER) ( 50 70 μM) and efficiently inhibited the estradiol (E 2 )-induced binding of the ER to its cognate DNA responsive element. The antagonist effects of LTr-1 also were exhibited in assays of endogenous pS2 gene expression and in cells transiently transfected with an estrogen-responsive reporter construct (pERE-vit-CAT). LTr-1 activated both binding of the aryl hydrocarbon (Ah) receptor to its cognate DNA responsive element and expression of the Ah receptor-responsive gene CYP1A1 . LTr-1 was a competitive inhibitor of CYP1A1-dependent ethoxyresorufin- O -deethylase (EROD) activity. In summary, these results demonstrated that LTr-1, a major in vivo product of I3C, could inhibit the proliferation of both estrogen-dependent and -independent breast tumor cells and that LTr-1 is an antagonist of estrogen receptor function and a weak agonist of Ah receptor function. IS - 5 JF - Biochemical Pharmacology SN - 00062952 EP - 834 TI - Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3′-diindolylmethane, a major in vivo product of dietary indole-3-carbinol VL - 58 SP - 825 KW - dim KW - indole AU - Chang, Y PY - 1999/09/01/ UR - http://dx.doi.org/10.1016/S0006-2952(99)00165-3 ER -