Differential effect of Bcl-xl over-expression on cell death of the monocytic leukemia cell line U937.

We studied the effect of over-expression of Bcl-xl on cell death of the monocytic cell line U937. Over-expression of Bcl-xl inhibits apoptotic changes induced by Etoposide including cytochrome-c release, caspase-3 activation and DNA fragmentation. However, Etoposide treatment resulted in cell death in U937 cells over-expressing Bcl-xl, which had a necrotic-like phenotype with no evidence of caspase-3 activation. On the other hand, Bcl-xl over-expression did not prevent U937 cell apoptotic cell death in response to the specific proteasome inhibitor Lactacystin. There was no significant change in the level of Bcl-xl or evidence of its cleavage. These results suggest that Bcl-xl over-expression does not confer protection against cell death in U937 cells and that Lactacystin utilizes an apoptotic pathway not susceptible to Bcl-xl inhibition.