(Sp)-8-CHLOROADENOSINE 3',5'-CYCLOPHOSPHATE INDUCED DIFFERENTIATION ON HUMAN LEUKEMIA HL-60 CELLS
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Abstract
(Sp)-octyl 8-chloroadenosine 3',5'-cyclophosphate(OCC),a newly synthesizedcAMP analog,strongly induced growth inhibition and differentiation in human leukemia HL-60 cells。The effects were dose and time-dependent and irreversible,In flow cytometry,OCC brought about ablock at the Gl phase of HL-60 cell cycle,Determined by incorporation assay,OCC was shown tostrongly inhibit DNA synthesis without affecting the synthesis of RNA and protein in HL-60 cells.OCC activated the protein kinase A(PKA)in the cytosol of HL-60 cells and inhibited its binding tocAMP,The activities of PKA in the cytosol of HL-60 cells treated with OCC were more significantlyincreased than those in control cells.It can be concluded that OCC binds itself to PKA in competitionwith cAMP and,as a result,activates PKA.
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