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- Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Cancer
Res 1998 Sep 1 58:17 3833-8
- Abstract
- Genistein, found in soy products, is a phytochemical with several
biological activities. In the current study,our research focused
on the estrogenic and proliferation-inducing activity of genistein.
We have demonstrated that genistein enhanced the proliferation
of estrogen-dependent human breast cancer (MCF-7) cells in vitro
at concentrations as low as 10 nM, with a concentration of 100
nM achieving proliferative effects similar to those of 1 nM estradiol.
Expression of the estrogen-responsive gene pS2 was also induced
in MCF-7 cells in response to treatment with a concentration of
genistein as low as 1 microM. At higher concentrations (above
20 microM), genistein inhibits MCF-7 cell growth. In vivo, we
have shown that dietary treatment with genistein (750 ppm) for
5 days enhanced mammary gland growth in 28-day-old ovariectomized
athymic mice, indicating that genistein acts as an estrogen in
normal mammary tissue. To evaluate whether the estrogenic effects
observed in vitro with MCF-7 cells could be reproduced in vivo,
MCF-7 cells were implanted s.c. in ovariectomized athymic mice,
and the growth of the estrogen-dependent tumors was measured weekly.
Negative control animals received the American Institute of Nutrition
(AIN)-93G diet, the positive control group received a new s.c.
estradiol (2 mg) pellet plus the AIN-93G diet, and the third group
received genistein at 750 ppm in the AIN-93G diet. Tumors were
larger in the genistein (750 ppm)-treated group than they were
in the negative control group, demonstrating that dietary genistein
was able to enhance the growth of MCF-7 cell tumors in vivo. Increased
uterine weights were also observed in the genistein-treated groups.
In summary, genistein can act as an estrogen agonist in vivo and
in vitro, resulting in the proliferation of cultured human breast
cancer cells (MCF-7) and the induction of pS2 gene expression.
Here we present new information that dietary genistein stimulates
mammary gland growth and enhances the growth of MCF-7 cell tumors
in ovariectomized athymic mice.
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