ROLE OF P53 AND APOPTOSIS IN SENSITIZATION OF CIS-DIAMMINEDICHLOROPLATINUM ANTITUMOR-ACTIVITY BY INTERLEUKIN-1-ALPHA IN OVARIAN-CARCINOMA CELLS

We have previously reported that interleukin-1 alpha (IL-1 alpha) sens itized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined interactions of IL-1 alpha with cispla tin in these ovarian cells. Treatment of cells with either IL-1 alpha or CDDP or combinations resulted in a significant accumulation of cell s in G1 phase and a concomitant decrease in the S phase of the cell cy cle. IL-1 alpha and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 alpha treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the gen omic DNA into internucleosomal sized DNA fragments which was further i ncreased in the presence of both agents in these cells. Taken together , these studies suggest that IL-1 alpha may kill ovarian NIH:OVCAR-3 t umor cells by inducing a blockade at G1/S of the cell cycle, downregul ating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 alpha with CDDP may involve the enhancement of p 53-dependent apoptosis.