I. Chen et al., ARYL-HYDROCARBON RECEPTOR-MEDIATED ANTIESTROGENIC AND ANTITUMORIGENICACTIVITY OF DIINDOLYLMETHANE, Carcinogenesis (New York. Print), 19(9), 1998, pp. 1631-1639
Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are co
mponents of cruciferous vegetables which exhibit antitumorigenic activ
ity associated with altered carcinogen metabolism and detoxification,
Diindolyl-methane (DIM) is a major acid-catalyzed metabolite of I3C fo
rmed in the gut that binds to the aryl hydrocarbon receptor (AhR) and
treatment of MCF-7 human breast cancer cells with 10-50 mu M DIM resul
ted in rapid formation of the nuclear AhR complex and induction of CYP
1A1 gene expression was observed at concentrations >50 mu M, Previous
studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TC
DD), a high affinity AhR ligand, inhibits 17 beta-estradiol (E2)-induc
ed responses in MCF-7 cells and growth of E2-dependent 7,12-dimethylbe
nzanthracene (DMBA)-induced mammary tumors in female Sprague-Dawley ra
ts. Results of this study show that like TCDD, DIM inhibits E2-induced
proliferation of MCF-7 cells, reporter gene activity in cells transie
ntly transfected with an E2-responsive plasmid (containing a frog vite
llogenin A2 gene promoter insert) and down-regulates the nuclear estro
gen receptor, Moreover, DIM (5 mg/kg every other day) also inhibits DM
BA-induced mammary tumor growth in Sprague-Dawley rats and this was no
t accompanied by induction of hepatic CYP1A1-dependent activity, Thus,
DLM represents a new class of relatively non-toxic AhR-based antiestr
ogens that inhibit Ea-dependent tumor growth in rodents and current st
udies are focused on development of analogs for clinical treatment of
breast cancer.