Premium
Short‐term suramin treatment followed by the removal of the drug induces terminal differentiation of HT29‐D4 cells
Author(s) -
Baghdiguian Stephen,
Verrier Bernard,
Marvaldi Jacques,
Fantini Jacques
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041500122
Subject(s) - suramin , biology , microbiology and biotechnology , cell culture , vacuole , pharmacology , chemistry , in vitro , biochemistry , genetics , cytoplasm
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 occurence 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.