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Dual anticancer activity of 8-Cl-cAMP: inhibition of cell proliferation and induction of apoptotic cell death.

Kim, SN; Kim, SG; Park, JH; Lee, MA; Park, SD; Cho-Chung, YS; Hong, SH
Biochemical and biophysical research communications, 273(2):404-410, 2000
Journal Title
Biochemical and biophysical research communications
8-Cl-cAMP induces apoptotic cell death in human cancer cells. To look at this more closely, we examined the changes in the levels of Bcl-2 family proteins during 8-Cl-cAMP-induced apoptosis of SH-SY5Y human neuroblastoma cells. Following the treatment with 8-Cl-cAMP, Bcl-2 was transiently down-regulated and Bad was increased continuously up to day 5. In addition, overexpression of Bcl-2 efficiently blocked the 8-Cl-cAMP-induced apoptosis, suggesting Bcl-2 family proteins may be involved in the 8-Cl-cAMP-induced apoptosis. The contribution of the apoptotic cell death and the inhibition of cell proliferation in the 8-Cl-cAMP-induced growth inhibition was closely monitored in the Bcl-2-overexpressing cells. Though the apoptosis was reduced significantly, no significant difference was observed in the inhibition of cell proliferation up to day 2 of 8-Cl-cAMP treatment. These results suggest that 8-Cl-cAMP exerts anticancer activity by two distinct mechanisms, i.e. , through the inhibition of cell proliferation as well as the induction of apoptosis. Supporting this notion was the observations that (1) suppression of apoptosis by zVAD did not abrogate 8-Cl-cAMP-induced inhibition of cell proliferation, and (2) 8-Cl-cAMP did not show additive inhibition of cell proliferation in RIIbeta-overexpressing cells.
MeSH terms
8-Bromo Cyclic Adenosine Monophosphate/*analogs & derivatives/pharmacologyAntineoplastic Agents/*pharmacologyApoptosis/*drug effectsCaspases/antagonists & inhibitorsCell Division/*drug effectsCell LineCyclic AMP-Dependent Protein Kinase RIIbeta SubunitCyclic AMP-Dependent Protein Kinases/metabolismGene ExpressionGenes, bcl-2HumansProto-Oncogene Proteins c-bcl-2/genetics/metabolismTumor Cells, Cultured
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Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
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