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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of insulin on key steps of carbohydrate metabolism were investigated in cultured HT29 colon cancer cells by two different approaches, i.e. incubation of the cells either in the absence or in the presence of glucose in the medium. In glucose-deprived cells, insulin decreased glycogen breakdown, but did not affect polysaccharide levels when glucose was present. Glycogen synthase became activated after insulin treatment in both conditions, even though the activation was more evident when glucose was omitted. No effect on glycogen phosphorylase activity was evident under our experimental conditions. In cells incubated with glucose, the hormone stimulated in a dose-dependent manner the rates of glucose uptake and lactate release. Concomitantly with the increase in glycolytic rate, insulin caused a strong increase in fructose 2,6-bisphosphate. This effect was not observed in the absence of glucose. It is concluded that the carbohydrate metabolism of cultured HT29 cells responds to insulin, making this biological model suitable for investigations in vitro on the mechanism of insulin action.
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PMID:Insulin controls key steps of carbohydrate metabolism in cultured HT29 colon cancer cells. 250 53

The functional properties of mitochondria bound hexokinase are compared in two subpopulations of the HT29 human colon cancer cell-line: (1) the HT29 Glc+ cells, cultured in the presence of glucose, which are poorly differentiated and highly glycolytic and (2) the HT29 Glc- cells, adapted to grow in a glucose-free medium, which are 'enterocyte-like' differentiated and less glycolytic when given glucose (Zweibaum et al. (1985) J. Cell Physiol. 122, 21-28). The activities of hexokinase, phosphofructokinase-1 and pyruvate kinase are found to be twice as high in Glc+ cells when compared to Glc- cells. Besides, the respiration rate is decreased in Glc+ cells compared to Glc- cells. These results correlate with the higher glycolytic rate in Glc+ cells. In many tissues, it has been shown that the binding of hexokinase to the mitochondrial outer membrane allows a preferential utilization of the ATP generated by oxidative phosphorylation which, in turn, is activated by immediate restitution of ADP. In highly glycolytic cancer cells, although a large fraction of hexokinase is bound to the mitochondria, the existence of such a channeling of nucleotides is still poorly documented. The rates of glucose phosphorylation by bound hexokinase were investigated in mitochondria isolated from both Glc+ and Glc- cells either with exogenous ATP or with ATP generated by mitochondria supplied with ADP and succinate (endogenous ATP). Diadenosine pentaphosphate (Ado2P5), oligomycin and carboxyatractyloside (CAT) were used in combination or separately as metabolic inhibitors of adenylate kinase, ATP synthase and ATP/ADP translocator, respectively. Exogenous ATP appears to be 6.5-times more efficient than endogenous ATP in supporting hexokinase activity in the mitochondria from Glc+ cells and only 1.8-times cells. The rate of oxidative phosphorylation being higher in mitochondria from Glc- cells, hexokinase activity is higher in this model when ATP is generated by respiration. Furthermore, in Glc+ mitochondria, the adenylate kinase reaction appears to be an important source of endogenous ATP for bound hexokinase, while, in Glc- mitochondria, hexokinase activity is almost totally dependent on the ATP generated by oxidative phosphorylation. This result might be explained by our previous finding that mitochondria from Glc+ cells lack contact sites between outer and inner membrane, whereas numerous contacts were observed in mitochondria from Glc- cells (Denis-Pouxviel et al. (1987) Biochim. Biophys. Acta 902, 335-348).
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PMID:Study on ATP-generating system and related hexokinase activity in mitochondria isolated from undifferentiated or differentiated HT29 adenocarcinoma cells. 252 30

1. Carbohydrate metabolism was studied in HT29 human colon cancer cells cultured in a glucose free medium supplemented with 2.8 mM inosine (HT29ino cells) in comparison with standard HT29 cells grown in the permanent presence of glucose (HT29Glc + cells) and with HT29Glc- cells which are adapted to grow permanently without glucose. 2. Inosine allows the standard cells to grow when glucose is lacking but surprisingly stops the growth of HT29Glc- cells. 3-mercaptopicolinate, an inhibitor of PEP-carboxykinase, does not hinder HT29ino cells to grow, which shows that gluconeogenesis from aspartate or pyruvate is not essential. It suggests that enough carbohydrate is supplied by the ribose moiety of inosine. 3. While standard HT29Glc + cells are highly glycolytic, it is not the case of HT29ino or HT29Glc- cells when glucose is given for few hours. When glucose is present for 24 hr or more, glycolytic rate increases in HT29ino cells and glycogen accumulates. 4. It is found that the pattern of enzymes activities related to carbohydrate metabolism in HT29ino cells is closer to that of HT29Glc + cells rather than to that of HT29Glc- cells. However, phosphofructokinase-1 activity, measured with saturating concentration of Fru-2,6-diP, is significantly lower in HT29ino cells. 5. Binding rate of hexokinase to mitochondria is similar in the three cell-lines. However, in HT29Glc- cells, bound hexokinase easily utilizes ATP generated by the mitochondria. By contrast, in HT29Glc+ and HT29ino cells, bound hexokinase is much more active with exogenous ATP, suggesting a functional defect in the mitochondria from these two latter cells.
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PMID:Carbohydrate metabolism in HT29 colon cancer cells cultured in a glucose free medium supplemented with inosine. 252 33

Thirteen colorectal cancer cell lines were established from 120 fresh colon cancer specimens. Expression of colon cancer-related antigens and blood group-related antigens on these cell lines were evaluated by Mixed Hemadsorption test (MHA) and Immune Adherence test (IA). The results were compared with the results of immunohistological analysis of the antigen expression in sections of the original tissues, and deletions of several blood group-related antigens in cell lines were observed. Colon cancer cell line HT-29, cultured in different lots of FCS or in different types of serum-free medium showed various antigen expression, suggesting the effect of culture medium on phenotypic expression. In glucose-free medium, HT-29 cells showed the characteristic "dome formation" which is typical of enterocytic differentiation forming brush borders in such cells. HT-29 cells cultured on bovine corneal endothelial extracellular matrix (BCE-ECM) coated plates showed similar enterocytic changes under phase-contrast microscope. Also, irradiated HT-29 cells cultured under 8-Azaguanine containing medium retained their strong resistance to 8-Azaguanine. These results suggest that these cancer cell lines might alter their phenotype, morphology, differentiation, growth pattern and drug sensitivity depending on the culture environment.
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PMID:[Alteration of phenotype, morphology and drug sensitivity in colon cancer cell lines under various culture conditions]. 273 80

Mucin from xenografts of LS174T human colon cancer cells was treated with anhydrous HF for 1 h at 0 degree C to give a product (HFA) with over 80% of the glucosamine and hexose removed, but retaining some galactosamine, and for 3 h at room temperature to give a product (HFB) devoid of carbohydrate. Rabbit antibodies against HFA bound to HFA much more than to HFB, and bound to native mucin to an intermediate extent. Antibodies to HFB bound to HFB more than to HFA, and did not bind to native mucin. Both HFA and native mucin bound a number of lectins, but HFB did not. By SDS/polyacrylamide-gel electrophoresis and size-exclusion h.p.l.c., native mucin and HFA are of apparent molecular mass greater than 400 kDa, whereas HFB is heterogeneous and of low molecular mass. On Western blots, antibody to HFA detected both high-molecular-mass mucin and a 90 kDa protein in homogenates of LS174T cells. Antibody to HFB detected a major 70 kDa band as well as higher-molecular-mass species. In tissue sections of normal colon and colon cancers, antibody to HFA showed both cytoplasmic and extracellular staining, whereas antibody to HFB generally stained only cytoplasmic antigens. These results indicate that anti-HFB antibody is specific for apo-mucin, whereas anti-HFA antibody is specific for GalNAc-apo-mucin.
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PMID:Deglycosylation of mucin from LS174T colon cancer cells by hydrogen fluoride treatment. 277 37

Effect of glutamine deprivation (GLN- medium) and of its replacement by 4mM ammonium chloride (GLN-/NH4+ medium) or by 4mM glutamate (GLN-/Gt+ medium) was studied on growth rate, morphology and metabolism of HT29 human colon cancer cells. Growth rates were modified as follows: at the first passage, growth of GLN- cells was strongly decreased (doubling time: 192 hr vs 32 hr in control cells grown in GLN+ medium); GLN-/NH4+ cells and GLN-/Gt+ cells were found to have doubling times of 72 and 70 hr, respectively. At the 8th passage, doubling times were decreased in all cases, being: 144 hr for GLN- cells, 60 hr for GLN-/NH4+ cells and 24 hr for GLN-/Gt+ cells, which indicates a capacity of adaptation of the cell-line to new culture conditions. GLN- cells and GLN-/NH4+ cells were found to exhibit an enterocytic type of differentiation (polarization of the cell layer with apical and cystic brush border and tight junctions); GLN-/Gt+ cells remained undifferentiated and comparable to control GLN+ cells. Glycogen level varied according to the phases of the culture, with a trend to lower level in glutamine deprived cells; glucose uptake and lactate production varied as a function of the medium composition and of the phases of the culture. At the 8th passage, all the glutamine deprived cells produced less lactate than control; GLN-/Gt+ cells were found to utilize less glucose than others.
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PMID:Effect of glutamine deprivation and glutamate or ammonium chloride addition on growth rate, metabolism and differentiation of human colon cancer cell-line HT29. 286 87

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 X 10(-6)M. Three different treatment protocols with FK (10(-5)M) 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 or 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.
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PMID:Enterocytic differentiation and glucose utilization in the human colon tumor cell line Caco-2: modulation by forskolin. 298 31

Studies on the regulation of the enterocytic differentiation of the human colon cancer cell line HT-29, which is differentiated in the absence (Glc-) but not in the presence of glucose (Glc+), have recently shown that the post-translational processing of sucrase-isomaltase and particularly its glycosylation vary as a function of cell differentiation (Trugnan G., Rousset, M., Chantret, I., Barbat, A., and Zweibaum, A. (1987) J. Cell Biol. 104, 1199-1205). Other studies indicate that in undifferentiated HT-29 Glc+ cells there is an accumulation of UDP-N-acetylhexosamine, which is involved in the glycosylation process (Wice, B. M., Trugnan, G., Pinto, M., Rousset, M., Chevalier, G., Dussaulx, E., Lacroix, B., and Zweibaum, A. (1985) J. Biol. Chem. 260, 139-146). The purpose of the present work is to investigate whether an overall alteration of protein glycosylation is associated with the inability of HT-29 cells to differentiate. At least three alterations are detected: (i) after a 10-min pulse, the incorporation of D-[2-3H]mannose in undifferentiated cells is severely reduced, compared to differentiated cells. (ii) After a 24-h period of labeling with D-[2-3H]mannose, undifferentiated cells accumulate more than 60% of the radioactivity in the high mannose glycopeptides, whereas differentiated HT-29 Glc- cells accumulate only 38%. (iii) The analysis of the high mannose oligosaccharides transferred "en bloc" from the lipid precursor shows that Man9,8-GlcNAc2 species accumulate in undifferentiated cells, whereas no such accumulation can be detected in differentiated cells. This glycosylation pattern is consistent with an impairment of the trimming of high mannose into complex glycans. It is concluded that N-glycan processing is correlated with the state of enterocytic differentiation of HT-29 cells.
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PMID:The processing of asparagine-linked oligosaccharides in HT-29 cells is a function of their state of enterocytic differentiation. An accumulation of Man9,8-GlcNAc2-Asn species is indicative of an impaired N-glycan trimming in undifferentiated cells. 336 Jul 73

The involvement of the mitochondrial bound hexokinase in aerobic glycolysis was investigated in two subpopulations of the HT 29 human colon cancer cell line: a poorly differentiated one with high aerobic lactate production (referred as undifferentiated or standard cells), and an enterocyte-like differentiated one with lower lactate production (referred as differentiated or Glc- cells). After mild digitonin treatment, 85% of the total cellular hexokinase activity remained in the particulate fraction in both cell types. In both cases mitochondria appeared to be tightly coupled but the Glc- cells exhibited a significantly higher oxidation rate in the presence of glucose. Electron microscopy of freeze-fractured cells revealed the absence of contacts between the two limiting mitochondrial membranes in the highly glycolytic standard cells, whereas the contacts were present in the Glc- cells. Furthermore, we investigated the functional relationship between bound hexokinase (as hexokinase-porin complex) and the inner compartment of mitochondria isolated from standard and Glc- HT 29 cells. In contrast to the differentiated cells the hexokinase in undifferentiated standard cells was not functionally coupled to the oxidative phosphorylation. This suggests that the high rate of lactate formation in neoplastic cells is not caused by an increase of particulate hexokinase activity but rather by a disregulation of the hexokinase-porin complex caused by the absence of contact sites between the two mitochondrial membranes. In agreement with this interpretation, the hexokinase-porin complex could be completely removed by digitonin treatment in standard HT 29 cells, while this was not possible in mitochondria from Glc- cells.
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PMID:Regulation of mitochondrial hexokinase in cultured HT 29 human cancer cells. An ultrastructural and biochemical study. 362 Apr 64

Using high-pressure liquid chromatography (HPLC) and gas-liquid chromatography/mass spectrometry (GLC/MS), we have confirmed the existence of several sialic acid modifications in the adult rat and human colon. The major O-acetylated sialic acid in both species is 9-O-acetyl-N-acetylneuraminic acid; N-glycolylneuraminic acid is a major component of the adult rat colon. Both of these major modifications were found to be developmentally regulated during the perinatal period in the rat. The N-glycolyl modification is present prenatally and disappears rapidly in the postnatal period. It reappears in the preweanling period, reaching levels at weaning comparable to those found prenatally. In contrast, the 9-O-acetyl modification is very low prenatally, and undergoes a marked increase shortly after birth in both the rat and human colon. The difference in the kinetics of appearance of the two modifications suggests that they are independently regulated. Regulation of these modifications seems to be influenced by exposure to bacterial by-products or environmental stimuli. The N-glycolyl modification in the rat colon reappeared at weaning, a time of major change in enteral colonic substances. Spontaneously aborted human fetuses, including three with intrauterine infection at 27, 33, and 35 wk of gestation, showed adult levels of O-acetylation in colonic tissue. Also, although O-acetylation in freshly isolated colon tumor specimens was only somewhat lower than that in the adult normal colon, all established colon cancer cell lines studied showed minimal O-acetylation.
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PMID:Developmental regulation of sialic acid modifications in rat and human colon. 362


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