Short-term suramin treatment followed by the removal of the drug induces terminal differentiation of HT29-D4 cells.
Suramin is an anti-cancer drug which induces the differentiation of the human colon cancer clone HT29-D4. Yet chronic suramin treatment of these cells eventually leads to a marked disturbance of the lysosomal system, which consists in an accumulation of hypertrophied autophagic vacuoles and the occurrence of lamellated inclusion bodies. We report here the effect of a prime treatment of HT29-D4 cells with suramin during various periods of time, followed by the removal of the drug and a subsequent culture in suramin-free medium. A prime treatment of cells in the presence of the drug for 2 days or 4 days was found ineffective to induce the organization of cells into polarized monolayers. On the contrary, a prime treatment of cells for 5 days is sufficient to allow the cellular organization to proceed normally toward a fully polarized monolayer, without any lysosomal damage. The cells did not require the continuous presence of suramin to develop an electrical resistance and a transepithelial potential difference. Moreover the basolateral localization of HLA class I molecules was achieved 9 days after the removal of the drug from the culture medium. Finally prime treatment of cells in the presence of suramin for times longer than 5 days induced the morphological, biochemical, and electrophysiological differentiation of HT29-D4 cells. However, in this case, severe lysosomal disturbances were constantly observed. These data demonstrate that the impaired lysosomal system is a post-differentiation event due to prolonged exposure of the cells to suramin. A metabolic analysis of HT29-D4 cells primed for various times with the drug showed that differentiated cells have a reduced glycolytic activity and this suggests an action of suramin at the level of autocrine growth factors which are known to regulate glucose uptake and degradation.
Baghdiguian
S
S
Institut de Chimie Biologique, Faculté St Charles, CNRS URA 202, Marseille, France.
Verrier
B
B
Marvaldi
J
J
Fantini
J
J
D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D003110:Colonic Neoplasms; D004594:Electrophysiology; D006019:Glycolysis; D006680:HLA Antigens; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects*; D008854:Microscopy, Electron; D013498:Suramin / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D013498:Suramin