Effect of 5‐Fluorouracil on Cell Cycle Regulatory Proteins in Human Colon Cancer Cell Line

We investigated the effects of 5‐fluorouracil (5‐FU) on cell cycle‐regulating proteins in RPMI 4788 cells. 5‐FU inhibited cell growth dose‐dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short‐term treatment (3 or 24 h) with 5‐FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A‐associated kinase activity assay showed that cyclin A‐cyclin‐dependent kinase (Cdk) 2 kinase activity was altered by 5‐FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5‐FU treatment was observed in three other human cancer cell lines, DLD‐1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5‐FU, and the cyclin A function and degradation mechanism remain normal.