A comparative study of the effects of genistein and 2-methoxyestradiol on the proteolytic balance and tumour cell proliferation


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The cytotoxicity of two compounds described as anti-angiogenic, the isoflavone genistein and the oestrogen metabolite 2-methoxyestradiol, has been studied in different human tumour cell


lines. Since the degradation of the extracellular matrix is one of the essential steps in angiogenesis, the potential modulatory effects of both compounds on the proteolytic balance in media


conditioned by different human tumour cells have been also investigated. The IC50 values for 2-methoxyestradiol were lower than those for genistein on all the cell lines tested. In all the


cell lines expressing measurable amounts of active enzymes, genistein induced a shift towards antiproteolysis in both matrix metalloproteinase/tissue inhibitor of metalloproteinase and


urokinase/plasminogen activator inhibitor proteolytic balances. On the other hand, 2-methoxyestradiol did not produce any clear net shift of the proteolytic balance, with the significant


exception of the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in WAC-2 cells, a neuroblastoma cell line with enhanced expression of the N-myc oncogene.


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Akiyama, T., Ishida, I., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., Shibuya, M. & Fuami, Y. (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem


262: 5592–5595.


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