Phenotypic differentiation‐linked growth inhibition in human leukemia cells by active vitamin D₃ analogues

Active vitamin D₃ induced phenotypic differentiation of the human promyelocytic leukemia cell line, HL‐60, cultured in serum‐free medium. Upon exposure to 10⁻¹‐10⁻⁷ M 1,25‐(OH)₂D₃ 1,24S‐(OH)₂D₃ or 1,24R(OH)₂D₃, monocyte‐granulocyte‐associated plasma membrane antigens of HL‐60 cells detected by monoclonal antibodies, OKM1, 63D3 and Mo2, quantitated by fluorescence‐activated cell sorter analysis, were increased time‐ and dose‐dependently. After expose to 1,25‐(OH)₂D₃, promotion of this antigenic expression was detected within 16 h, and the induction of differentiation continued until 96 h. The number of cells bearing transferrin receptors recognized by the monoclonal antibody, OKT9, and its density on the surface of HL‐60 cells were decreased symmetrically. These effects appeared in parallel with the inhibition of cell growth, poly(ADP‐ribose) content and de novo DNA‐RNA synthesis. These findings indicate that 1,24S‐(OH)₂D₃ stimulates differentiating induction of HL‐60 like 1,25‐(OH)₂D₃ in vitro and that the decrease of transferrin receptor is apparently correlated with the inhibition of proliferation.