The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor cells

The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor P-388 cells in a broad concentration range was studied. Cell proliferation,ras estimated by the metaphase frequency and the proportion of cells in S phase; cell death was determined from lysis, staining of cells with trypan blue, nuclear damage, percentage of cells with subdiploid DNA and the type of DNA fragmentation. It was shown that low concentrations of phospholipase A(2) and lipoxygenase inhibitors stimulated the proliferation of P-388 cells. At higher concentrations, the inhibitors suppressed cell proliferation by blocking the G(1)-S transition and induced cell death of the apoptosis type. Indomethacin, an inhibitor of cyclooxygenase, did not initiate cell death, nor did it affect the proliferation of P-388 cells at concentrations of up to 10 mu M. (C) 1995 Federation of European Biochemical Societies.