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ABSTRACT: Dietary genistin stimulates growth of estrogen-dependent
breast cancer tumors similar to that observed with genistein
[10/04/2001; Carcinogenesis]
The estrogenic soy isoflavone, genistein, stimulates growth of
estrogen-dependent human breast cancer (MCF-7) cells in vivo.
Genistin is the glycoside form of genistein and the predominant
form found in plants.
It is generally believed that genistin
is metabolized to the aglycone genistein in the lower gut. However,
it is unclear if the rate of metabolism of genistin to genistein
is sufficient to produce a level of genistein capable of stimulating
estrogen-dependent breast cancer cell growth.
Our hypothesis
was that dietary genistin would stimulate tumor growth similar
to that observed with genistein in athymic mice. To test this
hypothesis, genistin or genistein was fed to athymic mice containing
xenografted estrogen-dependent breast tumors (MCF-7).
Mice were
fed either genistein at 750 p.p.m. (parts per milllion) or genistin
at 1200 p.p.m., which provides equal molar concentrations of
aglycone equivalents in both diets. Tumor size was measured weekly
for 11 weeks.
At completion of the study, half of the animals
per treatment group were killed and tumors collected for evaluation
of cellular proliferation and estrogen-responsive pS2 gene expression.
Incorporation of bromo-deoxyuridine into cellular DNA was utilized
as an indicator of cellular proliferation.
Dietary genistin resulted
in increased tumor growth, pS2 expression and cellular proliferation
similar to that observed with genistein. The remaining mice were
switched to diets free of genistin and genistein.
When mice were
placed on isoflavone free diets, tumors regressed over a span
of 9 weeks. Next, we examined how effectively and where metabolism
of genistin to genistein occurred in the digestive tract.
We
present evidence that demonstrates conversion of genistin to
its aglycone form genistein begins in the mouth and then continues
in the small intestine. Both human saliva and the intestinal
cell-free extract from mice converted genistin to genistein.
In summary, the glycoside genistin, like the aglycone genistein,
can stimulate estrogen-dependent breast cancer cell growth in
vivo.
Removal of genistin or genistein from the diet caused tumors
to regress.
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