STUDY: Suppression of breast cancer cell growth with grape juice.

JOURNAL: Pharmaceutical Biol., 36:53-61, 1998.

AUTHORS: Chen, S., Sun, X.-Z., Kao, Y.-C., Kwon, A., Zhou, D., and Eng, E.

ABSTRACT: Breast Cancer Prevention with Phytochemicals in Grape Juice

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.