Involvement of diverse protein kinase C isoforms in the differentiation of ML-1 human myeloblastic leukemia cells induced by the vitamin D3 analogue KH1060 and the phorbol ester TPA

We reported previously that diverse combination of the vitamin D3 analogue KH1060 together with 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically induces the differentiation of ML-1 cells into mature macrophages. To investigate the mechanism involved in their interaction, we examined the role of protein kinase C (PKC) in the differentiation of ML-1 cells to mature macrophages. We found that the specific PKC inhibitor GF109203 suppressed the morphological change and the α-naphthyl acetate esterase activity induced in ML-1 cells by treatment with KH1060 plus TPA. This treatment increased the translocation of PKCα, PKCε, and PKCθ from cytosol to membranes. ML-1 cells treated with KH1060 alone increased translocation of PKCθ, whereas cells treated with TPA alone increased translocation of PKCα and PKCε. These data showed that in human myeloblastic leukemia cells, diverse isoforms of PKC, including PKCα, ε, and θ, participate in the regulation of cell differentiation.