Intracellular Ca2+ release mediates ursolic acid–induced apoptosis in human leukemic HL-60 cells

Abstract

The effect of ursolic acid (UA) on tumor cell apoptosis was investigated using HL-60 human promyelocytic leukemia cells as a model cellular system. Treatment with UA resulted in a concentration-dependent decreased 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 intracellular Ca2+ level was increased by treatment with UA. Intracellular Ca2+ inhibitors, such as intracellular Ca2+-release blockers (dantrolene, TMB-8 and ruthenium red) and an intracellular Ca2+ chelator (BAPTA/AM), significantly blocked the UA-induced increased intracellular Ca+ concentration. These inhibitors also blocked the effects of UA on cell viability and apoptosis. These results suggest that enhanced intracellular Ca2+ signals may be involved in UA-induced apoptosis in HL-60 cells.