The Caco-2 cell monolayer: usefulness and limitations

Bibliography

• Hidalgo IJ, Raub TJ, Borchardt RT. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 1989;96:736-49
   PubMed Web of Science ®Google Scholar
• Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man: fact or myth? Pharm Res 1997;14:763-6
   PubMed Web of Science ®Google Scholar
• Lennernäs H. Human jejunal effective permeability and its correlation with preclinical drug absorption models. J Pharm Pharmacol 1997;49:627-38
   PubMed Web of Science ®Google Scholar
• Hilgers AR, Conradi RA, Burton PS. Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm Res 1990;7:902-10
   PubMed Web of Science ®Google Scholar
• Mukherjee T, Squillantea E, Gillespieb M, Shao J. Transepithelial electrical resistance is not a reliable measurement of the Caco-2 monolayer integrity in Transwell. Drug Deliv 2004;11:11-8
   PubMed Web of Science ®Google Scholar
• Anderberg EK, Artursson P. Epithelial transport of drugs in cell culture. VIII. Effects of sodium dodecyl sulfate on cell membrane and tight junction permeability in human intestinal epithelial (Caco-2) cells. J Pharm Sci 1993;82:392-8
   PubMed Web of Science ®Google Scholar
• Smith J, Wood E, Dornish M. Effect of chitosan on epithelial cell tight junctions. Pharm Res 2004;21:43-9
   PubMed Web of Science ®Google Scholar
• Lindmark T, Kimura Y, Artursson P. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther 1998;284:362-9
   PubMed Web of Science ®Google Scholar
• Chirayath MV, Gajdzik L, Hulla W, et al. Vitamin D increases tight-junction conductance and paracellular Ca2+ transport in Caco-2 cell cultures. Am J Physiol 1998;274:G389-96
   PubMed Web of Science ®Google Scholar
• Watson CJ, Rowland M, Warhurst G. Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers. Am J Physiol Cell Physiol 2001;281:C388-97
   PubMed Web of Science ®Google Scholar
• Fine KD, Santa Ana CA, Porter JL, Fordtran JS. Effect of changing intestinal flow rate on a measurement of intestinal permeability. Gastroenterology 1995;108:983-9
   PubMed Web of Science ®Google Scholar
• Hilgendorf C, Ahlin G, Seithel A, et al. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 2007;35:1333-40
   PubMed Web of Science ®Google Scholar
• Sun D, Lennernas H, Welage LS, et al. Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res 2002;19:1400-16
   PubMed Web of Science ®Google Scholar
• Saito H, Motohashi H, Mukai M, Inui K. Cloning and characterization of a pH-sensing regulatory factor that modulates transport activity of the human H+/peptide cotransporter, PEPT1. Biochem Biophys Res Commun 1997;237:577-82
   PubMed Web of Science ®Google Scholar
• Sai Y, Kaneko Y, Ito S, et al. Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug Metab Dispos 2006;34:1423-31
   PubMed Web of Science ®Google Scholar
• Tamai I, Takanaga H, Maeda H, et al. Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids. Biochem Biophys Res Commun 1995;214:482-9
   PubMed Web of Science ®Google Scholar
• Hidalgo IJ, Borchardt RT. Transport of bile acids in a human intestinal epithelial cell line, Caco-2. Biochim Biophys Acta 1990;1035:97-103
   PubMed Web of Science ®Google Scholar
• Neimark E, Chen F, Li X, Shneider BL. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 2004;40:149-56
   PubMed Web of Science ®Google Scholar
• Elimrani I, Lahjouji K, Seidman E, et al. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 2003;284:G863-71
   PubMed Web of Science ®Google Scholar
• Hunter J, Jepson MA, Tsuruo T, et al. Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators. J Biol Chem 1993;268:14991-7
   PubMed Web of Science ®Google Scholar
• Gutmann H, Fricker G, Torok M, et al. Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake. Pharm Res 1999;16:402-7
   PubMed Web of Science ®Google Scholar
• Xia CQ, Liu N, Yang D, et al. Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells. Drug Metab Dispos 2005;33:637-43
   PubMed Web of Science ®Google Scholar
• Hirohashi T, Suzuki H, Chu XY, et al. Function and expression of multidrug resistance-associated protein family in human colon adenocarcinoma cells (Caco-2). J Pharmacol Exp Ther 2000;292:265-70
   PubMed Web of Science ®Google Scholar
• Bock-Hennig BS, Kohle C, Nill K, Bock KW. Influence of t-butylhydroquinone and beta-naphthoflavone on formation and transport of 4-methylumbelliferone glucuronide in Caco-2/TC-7 cell monolayers. Biochem Pharmacol 2002;63:123-8
   PubMed Web of Science ®Google Scholar
• Prime-Chapman HM, Fearn RA, Cooper AE, et al. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells. J Pharmacol Exp Ther 2004;311:476-84
   PubMed Web of Science ®Google Scholar
• Okuwaki M, Takada T, Iwayanagi Y, et al. LXR alpha transactivates mouse organic solute transporter alpha and beta via IR-1 elements shared with FXR. Pharm Res 2007;24:390-8
   PubMed Web of Science ®Google Scholar
• Lampen A, Bader A, Bestmann T, et al. Catalytic activities, protein- and mRNA-expression of cytochrome P450 isoenzymes in intestinal cell lines. Xenobiotica 1998;28:429-41
   PubMed Web of Science ®Google Scholar
• Baranczyk-Kuzma A, Garren JA, Hidalgo IJ, Borchardt RT. Substrate specificity and some properties of phenol sulfotransferase from human intestinal Caco-2 cells. Life Sci 1991;49:1197-206
   PubMed Web of Science ®Google Scholar
• Galijatovic A, Otake Y, Walle UK, Walle T. Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells–potential role in carcinogen bioinactivation. Pharm Res 2001;18:374-9
   PubMed Web of Science ®Google Scholar
• Peters WH, Roelofs HM. Time-dependent activity and expression of glutathione S-transferases in the human colon adenocarcinoma cell line Caco-2. Biochem J 1989;264:613-6
   PubMed Web of Science ®Google Scholar
• Schmiedlin-Ren P, Thummel KE, Fisher JM, et al. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3. Mol Pharmacol 1997;51:741-54
   PubMed Web of Science ®Google Scholar
• Brimer C, Dalton JT, Zhu Z, et al. Creation of polarized cells coexpressing CYP3A4, NADPH cytochrome P450 reductase and MDR1/P-glycoprotein. Pharm Res 2000;17:803-10
   PubMed Web of Science ®Google Scholar
• Fisher JM, Wrighton SA, Watkins PB, et al. First-pass midazolam metabolism catalyzed by 1alpha,25-dihydroxy vitamin D3-modified Caco-2 cell monolayers. J Pharmacol Exp Ther 1999;289:1134-42
   PubMed Web of Science ®Google Scholar
• Paine MF, Leung LY, Lim HK, et al. Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion. J Pharmacol Exp Ther 2002;301:174-86
   PubMed Web of Science ®Google Scholar
• Hochman JH, Chiba M, Nishime J, et al. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther 2000;292:310-8
   PubMed Web of Science ®Google Scholar
• Cummins CL, Jacobsen W, Christians U, Benet LZ. CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam. J Pharmacol Exp Ther 2004;308:143-55
   PubMed Web of Science ®Google Scholar
• Giuliano AR, Franceschi RT, Wood RJ. Characterization of the vitamin D receptor from the Caco-2 human colon carcinoma cell line: effect of cellular differentiation. Arch Biochem Biophys 1991;285:261-9
   PubMed Web of Science ®Google Scholar
• Bareis P, Kallay E, Bischof MG, et al. Clonal differences in expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase, of 25-hydroxyvitamin D(3)-24-hydroxylase, and of the vitamin D receptor in human colon carcinoma cells: effects of epidermal growth factor and 1alpha,25-dihydroxyvitamin D(3). Exp Cell Res 2002;276:320-7
   PubMed Web of Science ®Google Scholar
• Maier A, Zimmermann C, Beglinger C, et al. Effects of budesonide on P-glycoprotein expression in intestinal cell lines. Br J Pharmacol 2007;150:361-8
   PubMed Web of Science ®Google Scholar
• Huin C, Schohn H, Hatier R, et al. Expression of peroxisome proliferator-activated receptors alpha and gamma in differentiating human colon carcinoma Caco-2 cells. Biol Cell 2002;94:15-27
   PubMed Web of Science ®Google Scholar
• Chen F, Ma L, Dawson PA, et al. Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. J Biol Chem 2003;278:19909-16
   PubMed Web of Science ®Google Scholar
• Fallone F, Villard PH, Seree E, et al. Retinoids repress Ah receptor CYP1A1 induction pathway through the SMRT corepressor. Biochem Biophys Res Commun 2004;322:551-6
   PubMed Web of Science ®Google Scholar
• Thummel KE, Brimer C, Yasuda K, et al. Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Mol Pharmacol 2001;60:1399-406
   PubMed Web of Science ®Google Scholar
• Pfrunder A, Gutmann H, Beglinger C, Drewe J. Gene expression of CYP3A4, ABC-transporters (MDR1 and MRP1-MRP5) and hPXR in three different human colon carcinoma cell lines. J Pharm Pharmacol 2003;55:59-66
   PubMed Web of Science ®Google Scholar
• Echchgadda I, Song CS, Oh T, et al. The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase. Mol Endocrinol 2007;21:2099-111
   PubMed Web of Science ®Google Scholar
• Korjamo T, Monkkonen J, Uusitalo J, et al. Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear receptors. Pharm Res 2006;23:1991-2001
   PubMed Web of Science ®Google Scholar
• Bohets H, Annaert P, Mannens G, et al. Strategies for absorption screening in drug discovery and development. Curr Top Med Chem 2001;1:367-83
   PubMedGoogle Scholar
• Hubatsch I, Ragnarsson EG, Artursson P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc 2007;2:2111-9
   PubMed Web of Science ®Google Scholar
• Guidance for industry. Drug interaction studies – study design, data analysis and implications for dosing and labeling. FDA/CDER and CBER, 2006. Available from: http://www.fda.gov/cder/Guidance/6695dft.htm [Last accessed 17 January 2008]
   Google Scholar
• Saha P, Kou JH. Effect of bovine serum albumin on drug permeability estimation across Caco-2 monolayers. Eur J Pharm Biopharm 2002;54:319-24
   PubMed Web of Science ®Google Scholar
• Palm K, Luthman K, Ros J, et al. Effect of molecular charge on intestinal epithelial drug transport: pH-dependent transport of cationic drugs. J Pharmacol Exp Ther 1999;291:435-43
   PubMed Web of Science ®Google Scholar
• Tran TT, Mittal A, Gales T, et al. Exact kinetic analysis of passive transport across a polarized confluent MDCK cell monolayer modeled as a single barrier. J Pharm Sci 2004;93:2108-23
   PubMed Web of Science ®Google Scholar
• Rautio J, Humphreys JE, Webster LO, et al. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos 2006;34:786-92
   PubMed Web of Science ®Google Scholar
• Lennernäs H, Palm K, Fagerholm U, Artursson P. Comparison between active and passive drug transport in human intestinal epithelial (Caco-2) cells in vitro and human jejunum in vivo. Int J Pharm 1996;127:103-7
   Web of Science ®Google Scholar
• Parrott N, Lave T. Prediction of intestinal absorption: comparative assessment of GASTROPLUS and IDEA. Eur J Pharm Sci 2002;17:51-61
   PubMed Web of Science ®Google Scholar
• Matsson P, Bergstrom CA, Nagahara N, et al. Exploring the role of different drug transport routes in permeability screening. J Med Chem 2005;48:604-13
   PubMed Web of Science ®Google Scholar
• Englund G, Rorsman F, Ronnblom A, et al. Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells. Eur J Pharm Sci 2006;29:269-77
   PubMed Web of Science ®Google Scholar
• Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci 2006;78:2131-45
   PubMed Web of Science ®Google Scholar
• Artursson P, Magnusson C. Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells. J Pharm Sci 1990;79:595-600
   PubMed Web of Science ®Google Scholar
• Hochman JH, Fix JA, LeCluyse EL. In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine. J Pharmacol Exp Ther 1994;269:813-22
   PubMed Web of Science ®Google Scholar
• Polli JW, Wring SA, Humphreys JE, et al. Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 2001;299:620-8
   PubMed Web of Science ®Google Scholar
• Lentz KA, Polli JW, Wring SA, et al. Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res 2000;17:1456-60
   PubMed Web of Science ®Google Scholar
• Troutman MD, Thakker DR. Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. Pharm Res 2003;20:1200-9
   PubMed Web of Science ®Google Scholar
• Shepard RL, Cao J, Starling JJ, Dantzig AH. Modulation of P-glycoprotein but not MRP1- or BCRP-mediated drug resistance by LY335979. Int J Cancer 2003;103:121-5
   PubMed Web of Science ®Google Scholar
• den Ouden D, van den Heuvel M, Schoester M, et al. In vitro effect of GF120918, a novel reversal agent of multidrug resistance, on acute leukemia and multiple myeloma cells. Leukemia 1996;10:1930-6
   PubMed Web of Science ®Google Scholar
• de Bruin M, Miyake K, Litman T, et al. Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett 1999;146:117-26
   PubMed Web of Science ®Google Scholar
• Allen JD, van Loevezijn A, Lakhai JM, et al. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 2002;1:417-25
   PubMed Web of Science ®Google Scholar
• Gekeler V, Ise W, Sanders KH, et al. The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochem Biophys Res Commun 1995;208:345-52
   PubMed Web of Science ®Google Scholar
• Troutman MD, Thakker DR. Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res 2003;20:1210-24
   PubMed Web of Science ®Google Scholar
• Thiel-Demby VE, Tippin TK, Humphreys JE, et al. In vitro absorption and secretory quotients: practical criteria derived from a study of 331 compounds to assess for the impact of P-glycoprotein-mediated efflux on drug candidates. J Pharm Sci 2004;93:2567-72
   PubMed Web of Science ®Google Scholar
• Stephens RH, O'Neill CA, Warhurst A, et al. Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia. J Pharmacol Exp Ther 2001;296:584-91
   PubMed Web of Science ®Google Scholar
• Sun H, Pang KS. Permeability, transport, and metabolism of solutes in Caco-2 cell monolayers: a theoretical study. Drug Metab Dispos 2008;36:102-23
   PubMed Web of Science ®Google Scholar
• Bentz J, Tran TT, Polli JW, et al. The steady-state Michaelis-Menten analysis of P-glycoprotein mediated transport through a confluent cell monolayer cannot predict the correct Michaelis constant Km. Pharm Res 2005;22:1667-77
   PubMed Web of Science ®Google Scholar
• Kwon H, Lionberger RA, Yu LX. Impact of P-glycoprotein-mediated intestinal efflux kinetics on oral bioavailability of P-glycoprotein substrates. Mol Pharm 2004;1:455-65
   PubMedGoogle Scholar
• Cao X, Yu LX, Barbaciru C, et al. Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability. Mol Pharm 2005;2:329-40
   PubMed Web of Science ®Google Scholar
• Hochman JH, Yamazaki M, Ohe T, Lin JH. Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug–drug interactions with P-glycoprotein. Curr Drug Metab 2002;3:257-73
   PubMed Web of Science ®Google Scholar
• Doppenschmitt S, Spahn-Langguth H, Regardh CG, Langguth P. Radioligand-binding assay employing P-glycoprotein-overexpressing cells: testing drug affinities to the secretory intestinal multidrug transporter. Pharm Res 1998;15:1001-6
   PubMed Web of Science ®Google Scholar
• Taipalensuu J, Tavelin S, Lazorova L, et al. Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci 2004;21:69-75
   PubMed Web of Science ®Google Scholar
• Ohashi R, Tamai I, Yabuuchi H, et al. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther 1999;291:778-84
   PubMed Web of Science ®Google Scholar
• Giessmann T, May K, Modess C, et al. Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 2004;76:192-200
   PubMed Web of Science ®Google Scholar
• Gao J, Murase O, Schowen RL, et al. A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res 2001;18:171-6
   PubMed Web of Science ®Google Scholar
• Kalvass JC, Pollack GM. Kinetic considerations for the quantitative assessment of efflux activity and inhibition: implications for understanding and predicting the effects of efflux inhibition. Pharm Res 2007;24:265-76
   PubMed Web of Science ®Google Scholar
• Englund G, Hallberg P, Artursson P, et al. Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring. BMC Med 2004;2:8
   PubMedGoogle Scholar
• Mitin T, Von Moltke LL, Court MH, Greenblatt DJ. Levothyroxine up-regulates P-glycoprotein independent of the pregnane X receptor. Drug Metab Dispos 2004;32:779-82
   PubMed Web of Science ®Google Scholar
• Collett A, Tanianis-Hughes J, Warhurst G. Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro: a possible source of transporter mediated drug interactions? Biochem Pharmacol 2004;68:783-90
   PubMed Web of Science ®Google Scholar
• Hartley DP, Dai X, Yabut J, et al. Identification of potential pharmacological and toxicological targets differentiating structural analogs by a combination of transcriptional profiling and promoter analysis in LS-180 and Caco-2 adenocarcinoma cell lines. Pharmacogenet Genomics 2006;16:579-99
   PubMed Web of Science ®Google Scholar
• Ito S, Woodland C, Sarkadi B, et al. Modeling of P-glycoprotein-involved epithelial drug transport in MDCK cells. Am J Physiol 1999;277:F84-96
   PubMed Web of Science ®Google Scholar
• Tam D, Sun H, Pang KS. Influence of P-glycoprotein, transfer clearances, and drug binding on intestinal metabolism in Caco-2 cell monolayers or membrane preparations: a theoretical analysis. Drug Metab Dispos 2003;31:1214-26
   PubMed Web of Science ®Google Scholar
• Irie M, Terada T, Okuda M, Inui K. Efflux properties of basolateral peptide transporter in human intestinal cell line Caco-2. Pflugers Arch 2004;449:186-94
   PubMed Web of Science ®Google Scholar
• Gonzalez-Alvarez I, Fernandez-Teruel C, Garrigues TM, et al. Kinetic modelling of passive transport and active efflux of a fluoroquinolone across Caco-2 cells using a compartmental approach in NONMEM. Xenobiotica 2005;35:1067-88
   PubMed Web of Science ®Google Scholar
• Bourdet DL, Pollack GM, Thakker DR. Intestinal absorptive transport of the hydrophilic cation ranitidine: a kinetic modeling approach to elucidate the role of uptake and efflux transporters and paracellular vs. transcellular transport in Caco-2 cells. Pharm Res 2006;23:1178-87
   PubMed Web of Science ®Google Scholar
• Ho NF, Burton PS, Conradi RA, Barsuhn CL. A biophysical model of passive and polarized active transport processes in Caco-2 cells: approaches to uncoupling apical and basolateral membrane events in the intact cell. J Pharm Sci 1995;84:21-7
   PubMed Web of Science ®Google Scholar
• Tran TT, Mittal A, Aldinger T, et al. The elementary mass action rate constants of P-gp transport for a confluent monolayer of MDCKII-hMDR1 cells. Biophys J 2005;88:715-38
   PubMed Web of Science ®Google Scholar
• Adachi Y, Suzuki H, Sugiyama Y. Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res 2001;18:1660-8
   PubMed Web of Science ®Google Scholar
• Shirasaka Y, Sakane T, Yamashita S. Effect of P-glycoprotein expression levels on the concentration-dependent permeability of drugs to the cell membrane. J Pharm Sci 2008;97:553-65
   PubMed Web of Science ®Google Scholar
• Shirasaka Y, Kawasaki M, Sakane T, et al. Induction of human P-glycoprotein in Caco-2 cells: development of a highly sensitive assay system for P-glycoprotein-mediated drug transport. Drug Metab Pharmacokinet 2006;21:414-23
   PubMed Web of Science ®Google Scholar
• Watanabe T, Onuki R, Yamashita S, et al. Construction of a functional transporter analysis system using MDR1 knockdown Caco-2 cells. Pharm Res 2005;22:1287-93
   PubMed Web of Science ®Google Scholar
• Da Violante G, Zerrouk N, Richard I, et al. Short term Caco-2/TC7 cell culture: comparison between conventional 21-d and a commercially available 3-d system. Biol Pharm Bull 2004;27:1986-92
   PubMed Web of Science ®Google Scholar
• Sun H, Zhang L, Chow EC, et al. A catenary model to study the transport and metabolism of Baicalein, a bioactive flavonoid, in Caco-2 cell monolayer: Demonstration of substrate inhibition. J Pharmacol Exp Ther 2008 (under revision)
   Google Scholar
• Takara K, Takagi K, Tsujimoto M, et al. Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA. Biochem Biophys Res Commun 2003;306:116-20
   PubMed Web of Science ®Google Scholar
• Bock KW, Eckle T, Ouzzine M, Fournel-Gigleux S. Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells. Biochem Pharmacol 2000;59:467-70
   PubMed Web of Science ®Google Scholar
• Ebert B, Seidel A, Lampen A. Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate. Toxicol Sci 2007;96:227-36
   PubMed Web of Science ®Google Scholar
• Shimakura J, Terada T, Saito H, et al. Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor alpha. Am J Physiol Gastrointest Liver Physiol 2006;291:G851-6
   PubMed Web of Science ®Google Scholar
• Le Ferrec E, Lagadic-Gossmann D, Rauch C, et al. Transcriptional induction of CYP1A1 by oltipraz in human Caco-2 cells is aryl hydrocarbon receptor- and calcium-dependent. J Biol Chem 2002;277:24780-7
   PubMed Web of Science ®Google Scholar
• Chen X, Maiti S, Zhang J, Chen G. Nuclear receptor interactions in methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1). J Biochem Mol Toxicol 2006;20:309-17
   PubMed Web of Science ®Google Scholar
• Munzel PA, Schmohl S, Heel H, et al. Induction of human UDP glucuronosyltransferases (UGT1A6, UGT1A9, and UGT2B7) by t-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin in Caco-2 cells. Drug Metab Dispos 1999;27:569-73
   PubMed Web of Science ®Google Scholar
• Romero L, Higgins MA, Gilmore J, et al. Down-regulation of alpha class glutathione S-transferase by interleukin-1beta in human intestinal epithelial cells (Caco-2) in culture. Drug Metab Dispos 2002;30:1186-93
   PubMed Web of Science ®Google Scholar
• Naruhashi K, Tamai I, Inoue N, et al. Involvement of multidrug resistance-associated protein 2 in intestinal secretion of grepafloxacin in rats. Antimicrob Agents Chemother 2002;46:344-9
   PubMed Web of Science ®Google Scholar
• Moaddel R, Hamid R, Patel S, et al. Identification of P-glycoprotein substrates using open tubular chromatography on an immobilized P-glycoprotein column: Comparison of chromatographic results with Caco-2 permeability. Anal Chim Acta 2006;578:25-30
   PubMed Web of Science ®Google Scholar
• Gombar VK, Polli JW, Humphreys JE, et al. Predicting P-glycoprotein substrates by a quantitative structure-activity relationship model. J Pharm Sci 2004;93:957-68
   PubMed Web of Science ®Google Scholar
• Schrickx JA, Fink-Gremmels J. Danofloxacin-mesylate is a substrate for ATP-dependent efflux transporters. Br J Pharmacol 2007;150:463-9
   PubMed Web of Science ®Google Scholar
• Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G. Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res 2004;21:819-26
   PubMed Web of Science ®Google Scholar
• Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101:289-94
   PubMed Web of Science ®Google Scholar
• Luo FR, Paranjpe PV, Guo A, et al. Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells overexpressing efflux transporters Pgp, cMOAT, and MRP1. Drug Metab Dispos 2002;30:763-70
   PubMed Web of Science ®Google Scholar
• Yu L, Zeng S. Transport characteristics of zolmitriptan in a human intestinal epithelial cell line Caco-2. J Pharm Pharmacol 2007;59:655-60
   PubMed Web of Science ®Google Scholar
• Paine MF, Leung LY, Watkins PB. New insights into drug absorption: studies with sirolimus. Ther Drug Monit 2004;26:463-7
   PubMed Web of Science ®Google Scholar
• Karnaky KJ Jr, Hazen-Martin D, Miller DS. The xenobiotic transporter, MRP2, in epithelia from insects, sharks, and the human breast: implications for health and disease. J Exp Zoolog A Comp Exp Biol 2003;300:91-7
   PubMedGoogle Scholar
• Schrickx J, Lektarau Y, Fink-Gremmels J. Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells. Arch Toxicol 2006;80:243-9
   PubMed Web of Science ®Google Scholar
• Watanabe K, Jinriki T, Sato J. Effects of progesterone and norethisterone on cephalexin uptake in the human intestinal cell line Caco-2. Biol Pharm Bull 2004;27:559-63
   PubMed Web of Science ®Google Scholar
• Wenzel U, Kuntz S, Diestel S, Daniel H. PEPT1-mediated cefixime uptake into human intestinal epithelial cells is increased by Ca2+ channel blockers. Antimicrob Agents Chemother 2002;46:1375-80
   PubMed Web of Science ®Google Scholar
• Li F, Hong L, Mau CI, et al. Transport of levovirin prodrugs in the human intestinal Caco-2 cell line. J Pharm Sci 2006;95:1318-25
   PubMed Web of Science ®Google Scholar
• Tsuda M, Terada T, Irie M, et al. Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther 2006;318:455-60
   PubMed Web of Science ®Google Scholar
• Hadjiagapiou C, Schmidt L, Dudeja PK, et al. Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1. Am J Physiol Gastrointest Liver Physiol 2000;279:G775-80
   PubMed Web of Science ®Google Scholar
• Alrefai WA, Saksena S, Tyagi S, et al. Taurodeoxycholate modulates apical Cl-/OH-exchange activity in Caco2 cells. Dig Dis Sci 2007;52:1270-8
   PubMed Web of Science ®Google Scholar
• Tang F, Horie K, Borchardt RT. Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res 2002;19:773-9
   PubMed Web of Science ®Google Scholar
• Tang F, Horie K, Borchardt RT. Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res 2002;19:765-72
   PubMed Web of Science ®Google Scholar