Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane
A. Mcdougal et al., Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane, CANCER LETT, 151(2), 2000, pp. 169-179
This study investigates the antiestrogenic/estrogenic and antitumorigenic a
ctivities of the following diindolylmethane (DIM) derivatives: 4,4'-dichlor
o-, 5,5'-dichloro-, 6,6'-dichloro-, 5,5'-dibromo-, 5,5'-difluoro- and 5,5'-
dichloro-2,2'-dimethylDIM. E2-induced proliferation of T47D breast cancer c
ells was significantly inhibited (>90%) by the haloDIMs at concentrations o
f 5 or 10 muM, and only 4,4'-dichloroDIM alone increased cell proliferation
. With the exception of 5,5'-difluoroDIM, the remaining compounds also inhi
bited E2-induced growth of MCF-7 human breast cancer cells. DihaloDIMs (100
mg/kg/ day x 3) were not estrogenic in the immature female B6C3F1 mouse ut
erus; however, in animals co-treated with E2 (0.02 mug/mouse), 5,5'-dichlor
o- and 6,6'-dichloroDIM inhibited uterine progesterone receptor (PR) bindin
g and uterine peroxidase activity, whereas 5,5'-dichloro- and 5,5'-dichloro
-2,2'-dimethylDIM inhibited only the latter response. The antitumorigenic a
ctivities of the dihaloDIMs were determined by their inhibition of carcinog
en-induced mammary tumor growth in female Sprague-Dawley rats. 4,4'-Dichlor
o-, 5,5'-dibromo- and 6,6'-dichloroDIM, significantly inhibited mammary tum
or growth at doses of 1 mg/kg every second day, and no significant changes
in organ weights or liver and kidney histopathology were observed. These th
ree compounds were more active than DIM in the same in vivo assay. (C) 2000
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