Colonic carcinoma

Ralitrexed is a folate analog with greater selectivity. It easily crosses the cell membrane and undergoes polyglutamation. Within tissues, ralitrexed may be stored up to 29 days. It directly inhibits thymidylate synthase, the key enzyme for synthesizing thymidine triphosphate (TTP). The drug has been described to induce apoptosis in tumor cells. Ralitrexed is used for the treatment of colon carcinomas. 

Kirsten murine sarcoma (Ki-ras) Lung, colon carcinoma... 

KIRLIN w G, CAi J, DELONG M J, PATTEN E J and JONES D P (1999) Dietary compoimds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells , JNutr, 129 1827-35. 

OITATE M, NAKAKI R, KOYABU N, TAKANAGA H, MATSUO H, OHTANI H, SAWADA Y (2001) TranSCellular transport of genistein, a soybean-derived isoflavone, across human colon carcinoma cell line (Caco-2). Biopharm Drug Dispos. 22 23-9. 

In culture, the human colon carcinoma cell hne Caco-2 spontaneously differentiates at confluency into polarized cells with enterocyte-like characteristics. The principle of this approach consists of following the passage of the compound of interest from the apical or lumen-like sides to the basolateral or lymph-hke sides of Caco-2 cells, thus following the absorption of the compound per se. One obhgate step for fat-soluble nutrients such as carotenoids to cross the intestinal barrier is their incorporation into CMs assembled in the enterocytes. Under normal cell culture conditions, Caco-2 cells are unable to form CMs. When supplemented with taurocholate and oleic acid, Caco-2 cells were reported to assemble and secrete CMs. ... 

The physiological role of the ICOR is not clear and may be heterogeneous in the various tissues. In the thick ascending limb of the loop of Henle this channel appears to serve as the exit for CP at the basal cell pole [16,65,66], This conductive mechanism, therefore, is required for the reabsorption of Na and CP by this segment of the nephron [16]. In the rectal gland of Squalus acanthias a very similar channel is utilized for Na" and CP secretion. In these latter cells the CP-channel is present in the luminal membrane and is controlled by cytosolic cAMP [15,56,71]. It has been claimed that this kind of channel is also responsible for the secretion of CP in the colonic crypt cell, in colonic carcinoma cells and in respiratory epithelial cells [17,19,20,22]. Recent data have cast some doubt on this concept ... 

CP-channels with smaller conductance have first been noted in the rectal gland of Squalus acanthias by ourselves and in the colonic carcinoma cell line HT29 [61,73]. Later these types of 5-15 pS CP-channels were also found in pancreatic ducts, A6-cells and many other cells [74,75]. It is now claimed that this kind of channel is much more relevant than the ICOR for the pathophysiology of cystic fibrosis [12]. 

CP-channels with even smaller conductance have been described for the lacrimal and other exocrine glands [76,77]. These channels have a conductance of 1-2 pS. Unlike the ICOR-channel they appear to be blocked by millimolar concentrations of furosemide [77]. Most recent and only partially published data from my own laboratory obtained with the above modified nystatin technique [50,133,134] indicate that the respiratory epithelial cells and colonic carcinoma cells possess these types of small CP channels, and that these channels are involved in hormonal regulation of CP-conductance (cf. section 5). These CP-channels are regulated by cytosolic Ca. Hormonally induced increases in cytosolic Ca lead to an abrupt increase in the probability of these small CP-channels being open, yet they have no effect on the ICOR-channel. Data of this kind reinforce that the physiological importance of these small CP-channels may have been grossly underestimated. 

Fig. 3. Cellular model for NaCl secretion ([16] e.g., in a colonic carcinoma cell). The symbols have the following meaning = (Na" + K )-ATPase (J = Na 2Cl K -cotransporter - = ion...

Meanwhile we have shown that the excision activation of ICOR channels is due to disinhibition [72]. The respective inhibitor, operationally named cytosolic inhibitor (Cl), is present in the cytosol of placenta trophoblast cells HT29- and Tg4-colonic carcinoma cells and RE cells of normal and CF patients. The molecule has an apparent molecular weight of 700-1 500 Da it is amphiphilic heat stable and not digested by trypsin, proteases, nucleotidases, lipases or amylase [72]. Burc-khardt, Fromter and their collaborators [114] have confirmed our results and extracted a similar or identical Cl from kidney cortex. 

It has been known for some time that the Cl -conductance of epithelial cells can, in addition to its regulation via cAMP, be enhanced by increases in cytosolic Ca " (cf. Fig. 3). This has been shown with Ca -ionophores [120,121] or with hormones increasing cytosolic Ca such as carbachol, neurotensin, ATP, etc. [50,103,104]. Usually these agonists have dual effects. They increase the Cl - as well as the K" -conductance [104]. Stubs et al. [122] have shown that CF cells still increase their Cl -conductance in response to ATP. Another mechanism of Cl -channel activation has been described in whole-cell patches of colonic carcinoma and RE cells [123,124] when the cells are exposed to hypotonic media they swell and increase their Cl -conductance. This is a rather general phenomenon which is present in a lot of cells [11]. In their effort to reduce cell volume in hypotonic media (regulatory... 

Inhibition of DNA topo I activity in HCT 116 (human colon carcinoma) cells by CPT, CPT-11, SN-38, TPT, and EGCG (Table 8) ... 

The above three equations (Eqs. 10-12) for the different cell lines are very similar to each other, which suggests that the inhibition against DNA topo I is probably one of the most important antitumor mechanisms for these compounds (CPT, CPT-11, SN-38, TPT, and EGCG) against the three human colon carcinoma (HCT 116, VACO 241, and SW 480) cell lines. In these equations, the number of data points (four or five) is small, but the correlations are statistically significant. 

McKeever, J., Qureshi, A., Gorey, T., Kay, E., Byrne, P. and Hennessey, T.P.J. (1992). Azoxymethane induced free radical activity in rat colon carcinoma. Gastroenterology 102, A378. 

Li A, Varney ML, Singh RK. Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic potential. Clin Exp Metastasis 2004 21 571-579. 

Hidalgo, I. J. Kato, A. Borchardt, R. T., Binding of epidermal growth factor by human colon carcinoma cell (Caco-2) monolayers, Biochem. Biophys. Res. Commun. 160, 317-324 (1989). 

Royleanone, horminone, and acetyl horminone isolated from the roots of Salvia officinalis L. abrogated the survival of colon carcinoma cell Caco-2 and human hepatoma cell HepG2, cultured in vitro with induction of DNA breaks (48). 

The Caco-2 cell line was isolated from a human colon carcinoma, and has been characterized as one of the best in vitro models of intestinal epithelium. Indeed, in contrast to other intestinal cell lines, Caco-2 cells are able to constitute a homogenous monolayer and to spontaneously differentiate into polarized cells, highly similar to human mature enterocytes, after approximately 2 weeks of culture. Furthermore, the Caco-2 cells present microvillosities at the apical side and have a high transmembrane resistivity, which confirms the fact that the cells are confluent and link to one another via gap junctions. Finally, they can absorb different compounds, express many enzymes involved in intestinal metabolic pathways (Pinto et al. 1983, Musto et al. 1995, Salvini et al. 2002), and give reproducible in vitro results consistent with results obtained in in vivo studies (Artursson and Karlsson 1991). 

Pinto, M. et al. (1983). Enterocyte-like differentiation an polarizationof the human colon carcinoma cell line Caco-2 in culture. Biol. Cell 47 323-330. 

Das, S.K., Hashimoto, T., Shimizu, K., and Kanazawa, K. 2005. Fucoxanthin induces cell cycle arrest at GO/ Gl phase in human colon carcinoma cells through up-regulation of p21WAFl/Cipl. Biochim Biophys Acta 30 328-335. 

Hoffmann, R, Ji, H., Moritz, R. L., Connolly, L. M., Frecklington, D. F., Layton, M. J., Eddes, J. S., Simpson, R. J. (2001). Continuous free-flow electrophoresis separation of cytosolic proteins from the human colon carcinoma cell line LIM 1215 a non two-dimensional gel electrophoresis-based proteome analysis strategy. Proteomics 1(7), 807. 

Hiribarren, A., Heyman, M., L Helgouac h, A. and Desjeux, J.F. (1993) Effect of cytokines on the epithelial function of the human colon carcinoma cell line HT29 cll9A. Gut 34, 616-620. 

Borchardt, R. T., Characterization of the human colon carcinoma cell line (Caco-2) as a model for intestinal epithelial permeability, Gastroenterology 1989, 96, 736-749. 

M. D., Kedinger, M., Triadou, N., Dussaulx, E., Lacroix, B., Simon-Assman, P., Happen, K., Fogh, J., Zweibaum, A., Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture, Biol. Cell 1983, 47, 323-330. 

E., Brattain, M. G., Zweibaum, A., Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells a survey of twenty cell lines, Cancer Res. 1988, 48, 1936-1942. 

Brandsch, M., Miyamoto, Y., Ganapathy, V., Leibach, F. H., Expression and protein C-dependent regulation of peptide/H+ co-transport system in the Caco-2 human colon carcinoma cell line, Biochem. J. 1994, 299, 253-260. 

Grasset, E., Pinto, M., Dussaulx, E., Z WEI BAUM, A., Desjeux, J.-F., Epithelial properties of human colonic carcinoma cell line Caco-2 electrical parameters, Am. J. Physiol. 1984, 247, C260-C267. 

Cell line human colon carcinoma cells... 

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