Dexamethasone-induced killing of neoplastic cells of lymphoid derivation: lack of early calcium involvement.

The role of calcium influx in dexamethasone-induced fragmentation of DNA was studied in the glucocorticoid-sensitive human lymphoid line of T cell derivation (CEM-C7). Reduction of calcium content in the medium or the use of EGTA increased DNA fragmentation and appeared to slightly enhance the effect of dexamethasone. Incubation of isolated nuclei in the presence of high concentrations of calcium did not bring about significant DNA fragmentation. Calmidazolium, an antagonist of calmodulin dependent reactions did not reduce the sensitivity of CEM-C7 cells to dexamethasone nor did it modify the response to dexamethasone of the resistant CEM-C1 line. It appears that in contrast to rodent thymocytes, massive calcium influx is not per se responsible for the initiation of directed cell killing (apoptosis).

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.