The effect of prostacyclin agonists on the differentiation of phorbol ester treated human erythroleukemia cells.
Phorbol-12-myristate-13-acetate (PMA) induces megakaryocytopoeisis in human erythroleukemia (HEL) cells which is characterized by the increase in cell size, increase in nuclear polyploidization and expression of megakaryocyte marker, CD41. However, upon treatment with 100 nM of selective prostacyclin (IP) agonist beraprost inhibits the induced differentiation. Moreover, selective non-prostanoid IP agonist, BMY 45778 prevents PMA induced megakaryocytopoeisis in HEL cells similarly, while prostaglandin E(2) and specific EP(3) agonist sulprostone have no effect. Thus, IP receptor is involved. Furthermore, adenylate cyclase activator forskolin and cAMP analog dibutyryl-cAMP also prevented PMA induced megakaryocytopoeisis in HEL cells. Thus, IP agonists inhibition of PMA induced megakaryocytopoeisis in HEL cells may involve a cAMP dependent pathway.
Shen
Huang-Wei
HW
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
Chen
Yu-Lin
YL
Chern
Ching-Yuh
CY
Kan
Wai-Ming
WM
D000085:Acetates / Q000819:agonists; D002454:Cell Differentiation / Q000187:drug effects*; D011464:Epoprostenol / Q000819:agonists* / Q000031:analogs & derivatives; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000473:pathology; D010080:Oxazoles / Q000819:agonists; D010703:Phorbol Esters / Q000494:pharmacology*; D034061:Thrombopoiesis / Q000187:drug effects
D000085:Acetates; D010080:Oxazoles; D010703:Phorbol Esters; C084677:BMY 45778; C048081:beraprost; D011464:Epoprostenol