Suramin inhibits cell growth and glycolytic activity and triggers differentiation of human colic adenocarcinoma cell clone HT29-D4.
Suramin, a drug used in the treatment of trypanosomiasis and onchocerciasis inhibits growth factor-induced mitogenesis. In the present report, we show that suramin inhibits the growth of human colic adenocarcinoma cells HT29-D4 and rapidly induces their differentiation into enterocyte-like cells. As soon as 6 days after the addition of suramin (100 micrograms/ml) in the culture medium, the cells form a polarized monolayer of regular columnar cells with occluding junctions delimiting two distinct membrane domains (apical and basolateral) and an apical brush-border expressing alkaline phosphatase and sucrase-isomaltase. The process of differentiation is fully reversible when the drug is removed from the culture medium. We also show that suramin inhibits both glucose consumption and lactate production so that the glycolytic activity of the treated cells is lowered by 42%. This observation would shed some light on the complex mechanisms involved during the induction of HT29 cell differentiation when glucose is removed from the culture medium.
Fantini
J
J
Centre National de la Recherche Scientifique, Université de Provence, Marseille, France.
Rognoni
J B
JB
Roccabianca
M
M
Pommier
G
G
Marvaldi
J
J
D000230:Adenocarcinoma; D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms; D005455:Fluorescent Antibody Technique; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure
D013498:Suramin; D000469:Alkaline Phosphatase; D013394:Sucrase-Isomaltase Complex