Cyclic Adenosine Monophosphate Inhibits Ursolic Acid‐Induced Apoptosis via Activation of Protein Kinase A in Human Leukaemic HL‐60 Cells

Abstract

Abstract: This study was designed to investigate the effect of cAMP on ursolic acid‐induced apoptosis of HL‐60 cells. Ursolic acid decreased the viability of the cells in a dose‐dependent manner, which was revealed as an apototic process characterized by ladder‐pattern DNA fragmentation in agarose gel electrophoresis and segmented nuclei in DAPI‐sulpharhodamin 101 staining. Ursolic acid‐induced apoptosis of the cells was markedly inhibited by the addition of cAMP‐elevating agents including DB‐cAMP, CPT‐cAMP, 8‐Br‐cAMP and forskolin. These results were further evidenced by the fact that inhibitors of cAMP‐dependent protein kinase including H89 and KT5720 completely inhibited the cAMP‐mediated rescue of HL‐60 cells from ursolic acid‐induced apoptosis. In addition, differentiating agents of the cells such as dimethyl sulfoxide and retinoic acid did not affect the ursolic acid‐induced apoptosis of HL‐60 cells. These results suggest that signaling pathway of cAMP‐dependent activation of protein kinase A may affect the responsiveness of tumor cells upon ursolic acid.