Ca2+ and phorbol ester synergistically induce HL-60 differentiation.
Exposure of HL-60 cells to subthreshold concentrations of TPA caused monocytic differentiation only when cells were cotreated with the Ca2+ ionophore A23187. Phorbol ester dose-response curves for growth arrest and enzymatic markers of differentiation were shifted to lower concentrations when the ionophore was present. Expression of a monocyte/granulocyte cell surface antigen also occurred only when cells were treated with both agents. Similar effects were seen with other active but not inactive phorbol esters and with another Ca2+ ionophore. The Ca2+ component of phosphoinositide-based signalling may thus play a role in HL-60 differentiation.
D000954:Antigens, Surface / Q000032:analysis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000954:Antigens, Surface; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium