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  • Title: The role of cholesterol in the glucocorticoid-mediated inhibition of cell cycle progression in human acute lymphoblastic leukemia cells.
    Author: Cutts JL, Melnykovych G.
    Journal: Exp Cell Res; 1987 Jan; 168(1):95-104. PubMed ID: 3465537.
    Abstract:
    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.
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