Comparison of dexamethasone and lovastatin (mevinolin) as growth inhibitors in cultures of T-cell derived human acute leukemia lines (CEM).
Because previous studies have shown that a reduction of cholesterol synthesis is one of the earliest effects of dexamethasone on neoplastic lymphoid cells, a study was made to compare dexamethasone to lovastatin, a specific inhibitor of cholesterol synthesis, which acts on 3-hydroxy-3-methylglutaryl coenzyme A reductase. Two cell lines were used, both derived from human acute T-cell leukemia, one dexamethasone-sensitive (CEM-C7), the other dexamethasone-resistant (CEM-Cl). The results revealed a similar pattern of resistance and sensitivity of both lines to lovastatin, although only the dexamethasone effect was reversed by 1 microM RU 486, the antiglucocorticoid steroid. The cell killing by dexamethasone and lovastatin had the characteristics of apoptosis.
Bansal
N
N
Research Service 151, Veterans Administration Medical Center, Kansas City, MO 64128.
Houle
A G
AG
Melnykovych
G
G
D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D015458:Leukemia, T-Cell / Q000473:pathology*; D008148:Lovastatin / Q000494:pharmacology*; D008854:Microscopy, Electron; D015735:Mifepristone / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D015735:Mifepristone; D003907:Dexamethasone; D008148:Lovastatin