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Breast Cancer Prevention with Phytochemicals in Grape Juice
AUTHORS: Chen, S., Sun, X.-Z., Kao, Y.-C., Kwon, A., Zhou, D., and Eng, E.
Since phytochemicals such as flavones have been shown to be effective
inhibitors of aromatase, it is hypothesized that by inhibiting aromatase/estrogen
biosynthesis, fruit juices which contain flavones are chemopreventive agents for
breast cancer.
We have initially evaluated the hypothesis by determining
whether fruit juices repress aromatase activity. Our experiments revealed that
among seven fruit juices tested, red seedless grape juice was most effective in
inhibiting the activity of human placental aromatase.
Preliminary studies with a
nude mouse model have also been performed to determine the action of grape
juice in vivo. For this model, tumors form within one month after inoculating
MCF-7aro cells, aromatase expressing breast cancer cells, into eight-week old
female nude mice, and tumor formation can be suppressed by injecting the animals
with aromatase inhibitors such as 4-hydroxyandrostenedione.
We have found
that the average tumor size in mice fed (by gavage) with 0.5 ml of grape
juice/day is 30% that of the animals not fed with grape juice.
Based on results generated from our laboratory, we propose that grape juice
is a useful chemopreventive agent for breast cancer by suppressing
aromatase/estrogen biosynthesis.
We hope that a breast cancer prevention strategy using
grape juice can be developed based on results generated from the proposed
investigation. Experiments are being designed to determine the optimal conditions
for achieving breast cancer prevention.
Furthermore, we will determine the
scientific basis as to whether grape juice prevents the initiation and/or
progression of breast cancer or eradication of cancer cells by acting as an aromatase
inhibitor using two animal models, nude mice inoculated with MCF-7aro and the
NMU-induced tumor model in rats.
In addition, experiments will be performed to
identify the active components in grape juice that inhibit aromatase. The
latter experiments not only will lead to an understanding of the molecular basis
of aromatase inhibition by grape juice, but also allow us to design a potent
and selective breast cancer prevention strategy.
COMMENTARY: Aromatase converts androgen to estrogen. Aromatase is expressed
at a higher level in breast cancer tissue than in benign tissue.
In estrogen
biosynthesis in tumor tissue has been shown to play a role in promoting tumor
growth. Suppression of estrogen biosynthesis can be achieved by the prevention
of aromatase expression in breast tumors or by the inhibition of aromatase
activity.
There are several natural products that inhibit aromatase, but grape
juice certainly can rank as among the most tasty.
Pharmaceutical Biol., 36:53-61, 1998.
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