Coumarin modulates the cell-cycle progression of an MTV-EJras cell line.
The effects of coumarin (1,2-benzopyrone) on ras oncogene expression during the cell cycle of an MTV-EJras cell line was determined by flow cytometry. ras oncogene expression in cells was induced by dexamethasone 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 cells (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 cell-cycle progression of MTV-EJras cells and decreases ras expression in both G1 and S phases. These findings suggest a novel approach to the selective control of proliferation of malignant cells.
Kahn
J
J
Department of Medicine, San Francisco General Hospital, CA 94110.
Preis
P
P
Waldman
F
F
Tseng
A
A
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D003374:Coumarins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D011905:Genes, ras; D051381:Rats; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects
D003374:Coumarins; D003907:Dexamethasone; C030123:coumarin