Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation

The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H 2 receptors showed a rapid,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Brodsky, A., Davio, C., Shayo, C., Legnazzi, B.L., Barbosa, M., Lardo, M., Morelli, A., Baldi, A., Avalos, J.C.S., Rivera, E.
Formato: JOUR
Materias:
CAMP
Cell differentiation
Desensitization
Forskolin
Histamine
U937 cell
complement component C5a
cyclic AMP
dimaprit
forskolin
histamine
histamine H2 receptor
Myc protein
antigen expression
article
cell differentiation
cell level
cell line
cell proliferation
chemotaxis
concentration response
controlled study
dose response
drug effect
growth inhibition
priority journal
receptor down regulation
receptor occupancy
respiratory burst
Antigens, Neoplasm
Cell Differentiation
Cell Division
Cell Line
Chemotaxis
Cyclic AMP
Dose-Response Relationship, Drug
Genes, myc
Humans
Oxidation-Reduction
Tumor Cells, Cultured
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00142999_v350_n1_p121_Brodsky
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H 2 receptors showed a rapid, homologous desensitization, which might explain the dissimilar responses to histamine and dbcAMP. Forskolin induced an increase in cAMP levels in a concentration-dependent manner (EC 50 = 30 μM) for an extended period of at least 24 h. Forskolin but not histamine (up to 100 μM), also inhibited cell growth in a dose-dependent fashion (EC 50 = 22 μM). After 3 days of incubation, 75 μM forskolin induced U937 cell differentiation as judged by an increased rate of reduction of nitrobluetetrazolium (mean ± S.E.M.: 21.3 ± 6.6% in treated cells vs. 3.2 ± 1.9% in the control group, P < 0.001) and an augmented chemotactic response to complement 5a (C5a) (33.2 ± 5.9% in forskolin-treated vs. 0.34 ± 0.12% in control cells, P < 0.01). Furthermore, c-Myc levels decreased following forskolin treatment, while the histamine H2 receptor agonist dimaprit had no effect. We conclude that forskolin induces U937 cell differentiation through a sustained rise in cAMP levels.

Ejemplares similares