Transporters colon cancer

Another human colonic cancer cell line is T84 this develops monolayers of high TER ( 1000 Q cm2) when grown on permeable supports, but cells are not well differentiated and have been described as resembling a colonic crypt cell phenotype. Hence, these cells have been used mainly in studies of epithelial ion transport and are generally not considered to be adequate for drug transport studies, particularly with respect to carrier-mediated processes [10, 79, 82-84]. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

M. R. Ballestero, M. J. Monte, O. Briz, F. Jimenez, F. Gonzalez-San Martin and J. J. G. Marin, Expression of transporters potentially involved in the targeting of cytostatic bile-acid derivatives to colon cancer and polyps, Biochem. Pharmacol., 2006, 72, 729. 

Another human colonic cancer cell line is T84, which forms monolayers that are even tighter than those of the Caco-2. It has been described as resembling a colonic crypt cell phenotype. Hence, these cells have been used mainly in studies of epithelial ion secretion and are generally not considered to be adequate for drug transport studies, particularly with respect to carrier-mediated processes [13, 91, 92]. The rat intestinal epithelial cell line IEC-18 has been evaluated as a model to study small intestinal epithelial permeability. This cell line, which forms very leaky monolayers, was proposed to be a better model than the Caco-2 monolayers for evaluating the small intestinal paracellular permeation of hydrophilic molecules [93]. Importantly, the leaky tight junctions of the IEC-18 cells are a result of an undeveloped paracellular barrier lacking the perijunctional actin belt. In addition, the IEC-18 cells have minute expression of transporters [91, 93]. 

Clearly, transporters play a significant role in cancer therapy. However, in-depth knowledge about the activity of these transporters in colon cancer and more specifically in the various subpopulations of tumor cells is lacking. 

Besides the role of drug carriers in cancer, some membrane transporters have been demonstrated to act as tumor suppressor genes and be silenced by DNA methylation in colon cancer, and some transporters have been shown to be involved in EMT. As a consequence, membrane transporters may be differentially expressed between... 

Calcagno, A.M., Ludwig, J.A., Fostel, J.M., Gottesman, M.M. and Ambudkar, S.V. (2006) Comparison of drug transporter levels in normal colon, colon cancer, and Caco-2 cells impact on drug disposition and discovery. Molecular Pharmacology,... 

Fig. 4 (A) In vitro modeling of colon cancer (B) production of cord blood cells (C) astrocyte culture for cell-based therapy of Parkinson s disease and (D) placenta model using trophoblast cells for transport.

Three major cell models obtained from human colon cancers have been used HT-29, and T84, and Caco-2. HT-29 is a cell line capable of secreting mucin it has been used to study the effect of mucin on drug absorption. The T84 cell line does not express biochemical differentiation markers and is not particularly useful for studying drug transport. However, the T84 ceU line does express P-glycoprotein and can be used to study the role of this efflux pump. ... 

A twofold induction of the drug-metabolizing isoenzyme GYP1A2 was observed in human colon cancer cells (LS180) treated with horse chestnut extract. No effects on GYP3A4 or the transporter protein MDRl were observed (Brandin et al. 2007). 

In human colon cancer epithelial cells (Caco-2), the compound P57 exhibited a higher transport in the secretory direction than in the absorptive direction, and efflux was inhibited by selective inhibitors of multidrug resistance-associated proteins MRP1/MRP2 (MK-571) and P-gp (Madgula et al. 2008). 

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