The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells

Int J Cancer. 1997 Sep 17;72(6):1088-94. doi: 10.1002/(sici)1097-0215(19970917)72:6<1088::aid-ijc25>;2-#.


Retinoblastomas appear to be derived from a multipotential stem cell of the retina, due to alterations of the Rb1 gene. These tumors arise only within a discrete time frame during childhood, prior to terminal differentiation of the retinal precursor cells. Treatment of retinoblastoma cells with certain agents can induce a partial differentiation of cell types resembling those of the mature retina, such as rod and cone photoreceptors, glia, conventional neurons and pigment epithelia. We have tested the effects of 8-Cl-cAMP, a synthetic analog of cAMP which preferentially binds to and activates the RII subunit of protein kinase A on the Y-79 retinoblastoma cell line in vitro. Y-79 cells treated with 8-Cl-cAMP produced short, branching processes and showed a substantial increase in staining for neuron-specific enolase, a marker for conventional neuronal differentiation. In contrast, dibutyryl-cAMP gives a strong increase in the glial marker glial acidic fibrillary protein. Y-79 cell proliferation was strongly inhibited by 8-Cl-cAMP at concentrations as low as 5-25 microM. 8-Cl-cAMP significantly increased the rate of apoptosis of Y-79 cells in a dose-dependent manner. It also modulated expression of the RI regulatory subunit of intracellular cAMP-dependent protein kinase A, which is produced in abnormal quantities by Y-79 cells. A decrease in protein production was observed, with no clear effect on the RI subunit mRNA expression, suggesting that RI regulation occurs post-transcriptionally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives*
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Apoptosis / drug effects*
  • Bucladesine / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects*
  • Child
  • Cyclic AMP-Dependent Protein Kinases / biosynthesis
  • Cyclic AMP-Dependent Protein Kinases / chemistry
  • DNA Fragmentation
  • Eye Neoplasms
  • Humans
  • Kinetics
  • Macromolecular Substances
  • Phosphopyruvate Hydratase / biosynthesis
  • RNA, Messenger / biosynthesis
  • Retinoblastoma
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured


  • Macromolecular Substances
  • RNA, Messenger
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Bucladesine
  • 8-chloro-cyclic adenosine monophosphate
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphopyruvate Hydratase