Inhibition by Palmitoylcarnitine of Adhesion and Morphological Changes in HL-60 Cells Induced by 12-O-Tetradecanoylphorbol-13-acetate¹ Free

Effects of dl-palmitoylcarnitine (PC), an inhibitor of calciumactivated, phospholipid-dependent protein kinase (protein kinase C), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell differentiation were investigated in human promyelocytic leukemia cells (HL-60). TPA caused HL-60 cell adhesion concomitant with morphological changes, and an increase in acid phosphatase activity. The median effective concentration was 1 nm, which corresponded well to the dissociation constant of [³H]TPA binding to the cell extract. [³H]TPA binding to the cell extract was saturable and reversible. The maximal number of [³H]TPA-binding sites was 1.5 pmol/mg protein and a Hill coefficient was unity, indicating noncooperative interactions. PC, but neither palmitic acid nor dl-carnitine, inhibited the TPA-induced cell adhesion and morphological changes with the median inhibitory concentration of 1 µm, whereas a TPA-induced increase in acid phosphatase activity was not affected by 3 µm PC. Addition of PC 1 or 2 days after the addition of TPA was also effective in inhibiting the cell adhesion. Among various acylcarnitines, PC had the largest effect. [³H]TPA binding to the cell extract was not inhibited by PC at the concentration which was effective in inhibiting the TPA-induced cell adhesion. These results indicate that protein kinase C possibly mediates HL-60 cell differentiation induced by TPA.