MOMORDINS INHIBIT BOTH AP-1 FUNCTION AND CELL-PROLIFERATION

The activation of Jun/Fos is a crucial factor in transmiting the tumor promoting signal from the extracellular environment to .nuclear trans cription machinery. One of the final steps in signal transduction is t he binding of Jun/Fos to the AP-I site in order to express gene transc ription. Utilizing this concept, we screened about 100 extracts of nat ural plants to search for a Jun-Fos function inhibitor. The methanol e xtract of Ampelopsis radix reduced Jun/Foc retardation remarkably. The active principles of the extract were isolated and purified by repeat ed column chromatography and their structures were identified as olean olic acid glycosides known as momordin I, Id, and le. These compounds reduced the Jun/Fos-DNA interaction and their activities were quantita ted with liquid scintillation counting of corresponding bands. Among t hem, momordin I had the strongest inhibitory activity, with an IC50 va lue of 22.8 mu g/ml. The methanol extract and momordin I, Id and le al so showed cell cytotoxicity against human cancer cell lines. As expect ed from a gel shift assay, momordin I showed the strongest cytotoxicit y and its IC50 value was from 7.280 mu g/ml to 16.05 mu g/ml depending on the cell line. With these data, it may be concluded that the mecha nism of anticancer activity of momordin I comes from its inhibitory ef fect on the protein-DNA interaction. The in vivo test was done only wi th the methanol extract. The extract showed measurable anticancer acti vity against murine colon cancer. The wet tumor weight reduction rate was 17.73% at 90 mg/kg dose. We suggest that the Jun/Fos DNA interacti on results in cell cytotoxicity.