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

Gianfranco Fassina, Maria Grazia Aluigi, Susan Gentleman, Paul Wong, Tania Cai, Adriana Albini, Douglas M. Noonan

Research output: Contribution to journalArticle

Abstract

Retinoblastomas appear to be derived from a multipotential stem cell of the retina, due to alterations of the RbI 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, gila, 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 μM. 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 posttranscriptionally.

Original languageEnglish
Pages (from-to)1088-1094
Number of pages7
JournalInternational Journal of Cancer
Volume72
Issue number6
DOIs
Publication statusPublished - Sep 17 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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