Cyclic adenosine monophosphate inhibits ursolic acid-induced apoptosis via activation of protein kinase A in human leukaemic HL-60 cells.
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.
Choi
B M
BM
Department of Microbiology, Wonkwang University School of Medicine, Iksan, Chonbuk, Korea.
Park
R
R
Pae
H O
HO
Yoo
J C
JC
Kim
Y C
YC
Jun
C D
CD
Jung
B H
BH
Oh
G S
GS
So
H S
HS
Kim
Y M
YM
Chung
H T
HT
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000201:enzymology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013449:Sulfonamides; D014212:Tretinoin / Q000494:pharmacology; D014315:Triterpenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D002227:Carbazoles; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004121:Dimethyl Sulfoxide; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D011758:Pyrroles; D013449:Sulfonamides; D014212:Tretinoin; D014315:Triterpenes; D000097245:Ursolic Acid; C057416:KT 5720; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide