COUMARIN MODULATES THE CELL-CYCLE PROGRESSION OF AN MTV-EJRAS CELL-LINE

The effects of coumarin (1,2-benzopyrone) on ras oncogene expression d uring the cell cycle of an MTV-EJras cell line was determined by flow cytometry. ras oncogene expression in cells was induced by dexamethaso ne and increased fivefold during G1/G0 phase and threefold in S phase. Dexamethasone also increased the percentage of cells in S phase from 21% to 31%, compared to phosphate-buffered-saline-treated control cell s (P<0.01). Coumarin decreased the percentage of dexamethasone-treated cells in S phase from 31% to 19%, with a concomitant increase in the percentage of cells in G1/G0 compared to control levels. Coumarin also reduced ras expression (mean fluorescence) by 40% in G1/G0 phase and 30% in S phase. We conclude that coumarin significantly reduces the ce ll-cycle progression of MTV-EJras cells and decreases ras expression i n both G1 and S phases. These findings suggest a novel approach to the selective control of proliferation of malignant cells.