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

Autor: Susan Gentleman, Douglas M. Noonan, Tania Cai, Gianfranco Fassina, Adriana Albini, Paul Wong, M G Aluigi
Rok vydání: 1997
Předmět:
Zdroj: International Journal of Cancer. 72:1088-1094
ISSN: 1097-0215
0020-7136
Popis: 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 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 post-transcriptionally. Int. J. Cancer 72:1088–1094, 1997. © 1997 Wiley-Liss, Inc.
Databáze: OpenAIRE
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