Cyclic adenosine monophosphate inhibits quinolone alkaloid evocarpine-induced apoptosis via activation of protein kinase A in human leukaemic HL-60 cells.
Evocarpine, an isoquinolone alkaloid isolated from the fruit of Evodia rutaecarpa, was found to induce apoptotic cell death in promyelocytic leukaemia HL-60 cells in dose- and time-dependent manners. We investigated the involvement of protein kinase A during the evocarpine-induced apoptotic cell death. Evocarpine-induced apoptosis was markedly inhibited by treatment of the cells with dibutyryl-cyclic adenosine monophosphate. Similar results were obtained with other commonly used cyclic adenosine monophosphate analogues, chlorophenylthio-cyclic adenosine monophosphate and the intracellular cyclic adenosine monophosphate-elevating agent, forskolin. In contrast, pretreatment of HL-60 cells with KT5720, an inhibitor of cyclic adenosine monophosphate-dependent protein kinase A, abrogated the protective effects of cyclic adenosine monophosphate analogues and forskolin on evocrpine-induced apoptosis. These findings suggest that cyclic adenosine monophosphate-dependent activation of protein kinase A plays a crucial role in protecting HL-60 cells from the evocarpine-induced apoptotic cell death.
Kim
N Y
NY
Department of Microbiology and Immunology, Wonkwang University Medical School and Medicinal Resources Research Center of Wonkwang University, Iksan, Chonbuk, Korea.
Pae
H O
HO
Kang
T H
TH
Kim
Y C
YC
Lee
H S
HS
Chung
H T
HT
D017209:Apoptosis / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006801:Humans; D015363:Quinolones / Q000037:antagonists & inhibitors*
D015363:Quinolones; C059242:evocarpine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases