Effects of 1-beta-D-arabinofuranosylcytosine and phorbol ester on differentiation of human K562 erythroleukemia cells.
We have previously demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces hemoglobin synthesis in human K562 erythroleukemia cells. The present study extends these findings by demonstrating that ara-C treatment of K562 cells results in both increased heme synthesis and accumulation of alpha-, gamma-, epsilon-, and zeta-globin RNA. The results also demonstrate that ara-C enhances K562 cell surface expression of glycophorin. Furthermore, we demonstrate that phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) inhibits the effects of ara-C on heme production, accumulation of globin RNA, and glycophorin expression. The inhibitory effect occurs maximally when K562 cells are treated with TPA before undergoing ara-C-induced commitment to erythroid differentiation. These findings suggest that TPA inhibits an early step in the process required for ara-C to enhance expression of genes involved in the erythroid program.
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology*; D004261:DNA Replication; D005914:Globins / Q000235:genetics; D006021:Glycophorins / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood*; D007951:Leukemia, Myeloid / Q000097:blood*; D009693:Nucleic Acid Hybridization; D010704:Phorbols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D006021:Glycophorins; D010704:Phorbols; D012333:RNA, Messenger; D003561:Cytarabine; D006418:Heme; D005914:Globins; D013755:Tetradecanoylphorbol Acetate