CYCLIN A AND CDK2 KINASE-ACTIVITY ARE SUPPRESSED BY COMBINED TREATMENT WITH TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-ALPHA

We previously reported that combined treatment with tumor necrosis fac tor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) showed a synerg istic antitumor effect via regulation of cell cycle progression in the S phase. Here, we investigated the effect of the combined treatment w ith TNF-alpha and IFN-alpha on cell cycle regulating protein in RPMI 4 788 cells. Treatment with TNF-alpha or IFN-alpha alone showed no effec t on these proteins, however, the combined treatment showed suppressio n of cyclin A protein and its associated kinase activity. Furthermore, although the combined treatment inhibited Cdk2 kinase activity, the a mount of Cdk2 protein was not affected. These results suggested that T NF-alpha and IFN-alpha work together to suppress cyclin A and Cdk2 kin ase activity and to inhibit cell cycle progression in the S phase. (C) 1995 Academic Press. Inc.