EFFECTS OF OKADAIC ACID AND VANADATE ON TPA-INDUCED MONOCYTIC DIFFERENTIATION IN HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE HL-60

Treatment of HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TP A) (1-5 nM) induced inhibition of cell growth and the appearance of an adherent monocyte-like cell type in a dose- and time-dependent manner . The extent of TPA-induced monocytic differentiation was found to be markedly reduced by okadaic acid (OA) (35 nM). OA had to be present fo r the early 12 h during treatment with TPA to reduce the induction of monocytic differentiation. The majority of cells (80%) were non-adhere nt but morphologically resembled mature myelocytes or granulocytes aft er treatment with TPA (5 nM) in the presence of OA (35 nM). Vanadate ( VD), on the other hand, enhanced the extent of monocytic differentiati on induced by low-dose of TPA (1 nM), These results indicated that dep hosphorylation by tyrosine protein phosphatase and serine-threonine pr otein phosphatase may play an important role in the induction of monoc ytic and granulocytic differentiation.