Indo
le-3-carbino
l (I3C), a component of
Brassica vegetab
les, is under study as a preventiveagent of cancers of the breast and other organs. Fo
llowing ingestion, I3C is converted to a series ofo
ligomeric products that presumab
ly are responsib
le for the in vivo effects of I3C. We report the effectsof the major trimeric product, 5,6,11,12,17,18-hexahydrocyc
lonona[1,2-
b:4,5-
b':7,8-
b' ']triindo
le (CTr),on the estrogen receptor (ER) signa
ling pathways. Tumor-promoting effects of high doses of I3C may bedue to activation of ary
l hydrocarbon receptor (AhR)-mediated pathways; therefore, we a
lso examinedthe effects of CTr on AhR activated processes. We observed that CTr is a strong agonist of ER function.CTr stimu
lated the pro
liferation of estrogen-responsive MCF-7 ce
lls to a
leve
l simi
lar to that produced byestradio
l (E
2) but did not affect the growth of the estrogen-independent ce
ll line, MDA-MD-231. CTrdisp
laced E
2 in competitive-binding studies and activated ER-binding to an estrogen responsive DNAe
lement in ge
l mobi
lity shift assays with EC
50s of about 0.1
M. CTr activated transcription of an E
2-responsive endogenous gene and exogenous reporter genes in transfected MCF-7 ce
lls, a
lso with highpotency. CTr fai
led to activate AhR-mediated pathways, consistent with the
low-binding affinity of CTrfor the AhR reported previous
ly. Comparisons of the conformationa
l characteristics of CTr with other ER
ligands indicated a remarkab
le simi
larity with tamoxifen, a se
lective ER antagonist used as a breast cancertherapeutic agent and suggest an exce
llent fit of CTr into the
ligand-binding site of the ER.