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Flavonoids, Dietary-derived Inhibitors of Cell Proliferation and in Vitro Angiogenesis¹

Division of Hematology and Oncology, Children's Hospital, Ruprecht-Karls University, INF 150, 69120 Heidelberg, Germany [T. F., E. A., S. B., L. S.]; Institute of Histology and Embryology, Department of Morphology, University Medical Center 1121 Geneva 4, Switzerland [M. S. P., R. M.]; Department of Chemistry, Organic Chemistry Laboratory, P. O. Box 55, University of Helsink, FIN-00014 Helsinki, Finland [S. R., K. W.]; Department of Clinical Chemistry, Meilahti Hospital, University of Helsinki, SF-00290 Helsinki, Finland [H. A.]

Consumption of a plant-based diet can prevent the development and progression of chronic diseases associated with extensive neovascularization, including solid malignant tumors. In previous studies, we have shown that the plant-derived isoflavonoid genistein is a potent inhibitor of cell proliferation and in vitro angiogenesis. In the present study, we report that certain structurally related flavonoids are more potent inhibitors than genistein. Indeed, 3-hydroxyflavone, 3',4'-dihydroxyflavone, 2',3'-dihydroxyflavone, fisetin, apigenin, and luteolin inhibited the proliferation of normal and tumor cells, as well as in vitro angiogenesis, at half-maximal concentrations in the low micromolar range. We have previously demonstrated that genistein concentrations in the urine of subjects consuming a plant-based diet is 30-fold higher than in subjects consuming a traditional Western diet. The wider distribution and the more abundant presence of flavonoids in the plant kingdom, together with the present results, suggest that flavonoids may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumors.

¹ Work in Heidelberg was supported by grants from Deutsche Forschungsgemeinschaft, Kulemann-Stiftung. and Deutsche Krebshilfe; work in Geneva by Grant 31-43364.95 from the Swiss National Science Foundation; and work in Helsinki by grants from the Finnish Cancer Foundation and the Sigrid Juselius Foundation.

² To whom requests for reprints should be addressed, at Laboratory of Biological Chemistry. Medical School, University of Ioannina, 45110 Ioannina, Greece. Phone: (30)651 28388; Fax: (30)651 33442; E-mail: thfotsis@cc.uoi.gr.

³ Present address: Department of Hematology, Oncology and Endocrinology, Children's Hospital. University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.

Received 1/ 7/97. Accepted 5/13/97.

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