INTRACELLULAR CA2-INDUCED APOPTOSIS IN HUMAN LEUKEMIC HL-60 CELLS( RELEASE MEDIATES URSOLIC ACID)

The effect of ursolic acid (UA) on tumor cell apoptosis was investigat ed using HL-60 human promyelocytic leukemia cells as a model cellular system. Treatment with UA resulted in a concentration-dependent decrea sed cell viability assessed by MTT assay. UA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which UA induced cell death was through apoptosis. The intracellula r Ca2+ level was increased by treatment with UA. Intracellular Ca2+ in hibitors, such as intracellular Ca2+-release blockers (dantrolene, TMB -8 and ruthenium red) and an intracellular Ca2+ chelator (BAPTA/AM), s ignificantly blocked the UA-induced increased intracellular Ca2+ conce ntration. These inhibitors also blocked the effects of UA on cell viab ility and apoptosis. These results suggest that enhanced intracellular Ca2+ signals may be involved in UA-induced apoptosis in HL-60 cells. (C) 1997 Wiley-Liss, Inc.