Cell differentiation and cell cycle effects on human promyelocytic leukemia cells induced by 12-O-tetradecanoylphorbol-13-acetate.

As has been reported, doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) as small as 1 to 100 ng/ml induced human promyelocytic leukemia HL-60 cells to differentiate terminally into macrophage-like cells rather than toward cells of the granulocytic series. This differentiation was accompanied by the appearance of monocyte/macrophage markers and by the disappearance of myeloid markers from the view point of enzyme cytochemistry. Contrasted to untreated HL-60 cells, TPA-treated cells increased in cell size and showed increased phagocytotic activities against opsonized sheep blood red cells and activated yeast. Nitroblue tetrazolium-positive cells increased rapidly after TPA exposure. The alterations of the cell cycle traverse of HL-60 cells by TPA were analyzed by [3H]thymidine autoradiography, flow microfluorimetry, and mitotic cell counting. TPA sequentially caused (a) inhibition of cells to move from G1 to S near G1/S boundary in G1; (b) temporary inhibition in G2; (c) growth arrest of most cells in G1 within 2 to 3 days after TPA exposure.