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Cyclin A and Cdk2 kinase activity are suppressed by combined treatment with tumor necrosis factor-alpha and
K Satomoto1, M Haisa, Y Naomoto
1First Department of Surgery, Okayama University Medical School, Japan.
Abstract:
We previously reported that combined treatment with tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) showed a synergistic antitumor effect via regulation of cell cycle progression in the S phase. Here, we investigated the effect of the combined treatment with TNF-alpha and IFN-alpha on cell cycle regulating protein in RPMI 4788 cells. Treatment with TNF-alpha or IFN-alpha alone showed no effect on these proteins, however, the combined treatment showed suppression of cyclin A protein and its associated kinase activity. Furthermore, although the combined treatment inhibited Cdk2 kinase activity, the amount of Cdk2 protein was not affected. These results suggested that TNF-alpha and IFN-alpha work together to suppress cyclin A and Cdk2 kinase activity and to inhibit cell cycle progression in the S phase.