The role of cholesterol in the glucocorticoid-mediated inhibition of cell cycle progression in human acute lymphoblastic leukemia cells.
Two glucocorticoid receptor-containing clones of human acute lymphoblastic leukemia, one (CEM-C7) sensitive and one (CEM-C1) resistant to dexamethasone (dex) were studied in an effort to identify the time course of the biochemical changes responsible for dex-induced growth inhibition of CEM-C7 cells. Cells were synchronized by treatment with 0.25 mM (C7) or 0.50 mM (C1) thymidine for 12 h followed by 0.025 micrograms/ml (C7) or 0.050 micrograms/ml (C1) colcemid for 12 h, then released either in the presence or absence of 1 microM dex. The inhibition of cellular proliferation which occurs at 48 h after release in the dex-treated CEM-C7 cells was preceded by an inhibition of acetate incorporation into cholesterol, first evident at 24 h, inhibition of protein synthesis at 30 h, and the development of a cell cycle block in G1 at 36 h. No inhibition of any of these parameters was seen in the resistant CEM-C1 cells. Thus the inhibition of cholesterol synthesis in the sensitive cells may be one of the earliest parameters affected by glucocorticoids.
Cutts
J L
JL
Melnykovych
G
G
D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D003703:Demecolcine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000473:pathology*; D014176:Protein Biosynthesis; D013936:Thymidine / Q000494:pharmacology
D003907:Dexamethasone; D002784:Cholesterol; D013936:Thymidine; D003703:Demecolcine