Vitamin D-3 analogue KH1060 combined with TPA synergistically induces mature macrophages in human myeloblastic leukemia ML-1 cells

A human myeloblastic leukemia cell line, ML-1, was induced to differentiate along the monocytic lineage following exposure to a 1,25-dihydroxyvitamin D3 analogue, 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-dihydroxyvitamin D3 (K H1060) or 12-O-tetradecanoylphorbol-13-acetate (TPA). The combination of KH 1060 and TPA synergistically induced differentiation of ML-1 cells into mat ure macrophages with multinuclei. Maturation was also observed in other dif ferentiation characteristics such as phagocytic activity, a-naphthyl acetat e esterase activity, and expression of surface antigen CD14. Differentiated ML-1 cells showed attenuation of telomerase activity and cessation of prol iferating activity based on evaluation of the expression of genes related t o cell growth potential. Remarkable synergism was observed in TNF productio n. Treatment with TPA prior to KH1060 resulted in only slight production gf TNF; however, treatment with KH1060 preceding TPA induced a substantial am ount of TNF.