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

• Published in: European journal of pharmacology 1998-05, Vol.350 (1), p.121-127
• Main Authors: Brodsky, Andrés, Davio, Carlos, Shayo, Carina, Lemos Legnazzi, Bibiana, Barbosa, Marcos, Lardo, Mabel, Morelli, Adrián, Baldi, Alberto, Sanchez Avalos, Julio César, Rivera, Elena
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - metabolism; Biological and medical sciences; cAMP; Cell differentiation; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell Division - drug effects; Cell Line; Cell physiology; Chemotaxis - drug effects; Colforsin - pharmacology; Cyclic AMP - metabolism; Desensitization; Dose-Response Relationship, Drug; Forskolin; Fundamental and applied biological sciences. Psychology; Genes, myc - drug effects; Genes, myc - physiology; Histamine; Histamine - metabolism; Humans; Molecular and cellular biology; Oxidation-Reduction; Tumor Cells, Cultured; U937 cell
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00227-1

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