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.