Enterocytic differentiation and glucose utilization in the human colon tumor cell line Caco-2: Modulation by forskolin
Article first published online: 4 FEB 2005
Copyright © 1985 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 123, Issue 3, pages 377–385, June 1985
How to Cite
Rousset, M., Laburthe, M., Pinto, M., Chevalier, G., Rouyer-Fessard, C., Dussaulx, E., Trugnan, G., Boige, N., Brun, J.-L. and Zweibaum, A. (1985), Enterocytic differentiation and glucose utilization in the human colon tumor cell line Caco-2: Modulation by forskolin. J. Cell. Physiol., 123: 377–385. doi: 10.1002/jcp.1041230313
- Issue published online: 4 FEB 2005
- Article first published online: 4 FEB 2005
- Manuscript Accepted: 10 JAN 1985
- Manuscript Received: 4 OCT 1984
The human colon cancer line Caco-2 exhibits after confluency a concomitant increase of glycogen accumulation and an enterocytic differentiation. The purpose of this work was to investigate whether forskolin (FK), an activator of adenylate cyclase, would induce a permanent glycogenolysis and, if so, whether it would result in modifications of the differentiation pattern of the cells. FK activates adenylate cyclase in Caco-2 cells with an ED50 of 7 × 10−6M. Three different treatment protocols with FK (10−5M) were applied: (1) the cells were treated during all the time in culture (20 days); (2) the treatment was started after confluency; (3) the treatment was interrupted after confluency. The presence of FK results in a permanent stimulation of cAMP accumulation (10 to 20 fold the basal values) and in a permanently reduced glycogen content (30 to 50% of the control values). The rates of glucose consumption are increased three and five fold in protocols 1 and 3 respectively. These metabolic changes are associated with morphological changes (tightening of the intercellular spaces and shortening of the brush border microvilli) and with a dual inhibition of the activities of brush border hydrolases: (a) an inhibition of the post-confluent increase of activity of sucrase, aminopeptidase N and alkaline phosphatase in the brush border enriched fraction; (b) an inhibition of the post-confluent increase of activity of sucrase in the cell homogenate. A comparison of the results obtained in each protocol shows that the morphological modifications and the decrease of the enzyme activities in the brush border fraction are regularly associated with an increased cAMP accumulation, whereas the inhibition of the differentiation of sucrase is a direct consequence of the increase in glucose consumption and decrease in glycogen stores.