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 ruta ecarpa, was found to induce apoptotic cell death in promyelocytic leukaemia HL-60 cells in dose- and time-dependent manners. We investigated the invol vement of protein kinase A during the evocarpine-induced apoptotic cell dea th. 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 cycl ic adenosine monophosphate-elevating agent, forskolin. In contrast, pretrea tment of HL-60 cells with KT5720, an inhibitor of cyclic adenosine monophos phate-dependent protein kinase A, abrogated the protective effects of cycli c adenosine monophosphate analogues and forskolin on evocrpine-induced apop tosis. These findings suggest that cyclic adenosine monophosphate-dependent activation of protein kinase A plays a crucial role in protecting HL-60 ce lls from the evocarpine-induced apoptotic cell death.