[(Sp)-8-chloroadenosine 3',5'-cyclophosphate induced differentiation on human leukemia HL-60 cells]

(Sp)-octyl 8-chloroadenosine 3',5'-cyclophosphate(OCC), a newly synthesized cAMP 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 a block at the G1 phase of HL-60 cell cycle. Determined by incorporation assay, OCC was shown to strongly 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 to cAMP. The activities of PKA in the cytosol of HL-60 cells treated with OCC were more significantly increased than those in control cells. It can be concluded that OCC binds itself to PKA in competition with cAMP and, as a result, activates PKA.