Objective    To investigate the mechanism of ursolic acid-induced apoptosis in human leukemia cells.     Methods    U937 cells were exposed to ursolic acid (UA) at various concentrations for 6 h and 12 h

or at 20 μmol/L for different time intervals. Cells were stained with Annexin V/PI

and their apoptosis was determined through flow cytometry. Total protein extracts were prepared and subjected to Western blot assay using antibodies against PARP

C-Caspase-3

C-Caspase-9

Mcl-1

Bcl-2

Bcl-xL

Bax

and Bad. Parallel studies were performed in human leukemia cell lines Jurkat and HL-60.     Results    Exposure of U937 cells to UA resulted in increase in apoptosis in dose and time-dependent manners. We found that UA-induced lethality was associated with Caspase activation and PARP cleavage

and that UA-induced apoptosis was proceeded by the downregulation of Mcl-1. Jurkat and HL-60 leukemia cells in parallel studies exhibited apoptosis after UA exposure similar to those observed in U937 cells

although HL-60 cells were less sensitive than U937 cells in UA-induced apoptosis

PARP degradation as well as Caspases activation.     Conclusion    UA induces apoptosis in human leukemia cells through a process that involves Mcl-1 downregulation

followed by Caspase activation and PARP degradation.