Intracellular Ca2+ release mediates ursolic acid-induced apoptosis in human leukemic HL-60 cells.
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.
Baek
J H
JH
Department of Molecular Biology, Pusan National University, Korea.
Lee
Y S
YS
Kang
C M
CM
Kim
J A
JA
Kwon
K S
KS
Son
H C
HC
Kim
K W
KW
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D014315:Triterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D002118:Calcium; D002121:Calcium Channel Blockers; D004273:DNA, Neoplasm; D014315:Triterpenes; D000097245:Ursolic Acid