[(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.
Su
J
J
National Research Laboratories of Natural and Biomimetic Drugs, Beijing Medical University.
Yang
X B
XB
Wang
L X
LX
Xu
B
B
Zhang
L H
LH
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018922:HL-60 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases