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Polarized transport of docetaxel and vinblastine mediated by P-glycoprotein in human intestinal epithelial cell monolayers. 1994

P Wils, and V Phung-Ba, and A Warnery, and D Lechardeur, and S Raeissi, and I J Hidalgo, and D Scherman
UMR133 CNRS/RPR Rhône-Poulenc Rorer Centre de Recherche de Vitry-Alfortville, France.

The expression of the multidrug transporter P-glycoprotein has been studied in two human intestinal epithelial cell lines. No functional expression of P-glycoprotein was found in the differentiated HT29-18-C1 cell line. The expression of P-glycoprotein in the Caco-2 cell line was very high, as judged by immunoblotting and by active efflux of vinblastine. The polarized transport of vinblastine in the basolateral to apical direction was temperature and energy dependent, and was reduced by P-glycoprotein inhibitors such as verapamil, chlorpromazine and reserpine. This adds further evidence that the polarized transport of vinblastine across Caco-2 monolayers is mediated by P-glycoprotein. The anticancer drug docetaxel (Taxotere) was transported in a polarized manner: basolateral to apical permeability was 20-fold higher than in the reverse direction. This polarized transport was inhibited by verapamil, chlorpromazine and reserpine, thus demonstrating that docetaxel is a substrate of P-glycoprotein. The implications of these results for the pharmacokinetics and toxicity of taxoids are discussed.

UI MeSH Term Description Entries
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077143 Docetaxel A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER. Docetaxel Anhydrous,Docetaxel Hydrate,Docetaxel Trihydrate,Docetaxol,N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol,NSC 628503,RP 56976,RP-56976,Taxoltere Metro,Taxotere,N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol,RP56976
D000972 Antineoplastic Agents, Phytogenic Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
D001693 Biological Transport, Active The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy. Active Transport,Uphill Transport,Active Biological Transport,Biologic Transport, Active,Transport, Active Biological,Active Biologic Transport,Transport, Active,Transport, Active Biologic,Transport, Uphill
D014747 Vinblastine Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.) Vincaleukoblastine,Cellblastin,Lemblastine,Velban,Velbe,Vinblastin Hexal,Vinblastina Lilly,Vinblastine Sulfate,Vinblastinsulfat-Gry,Sulfate, Vinblastine
D015151 Immunoblotting Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies. Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings
D017239 Paclitaxel A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death. 7-epi-Taxol,Anzatax,Bris Taxol,NSC-125973,Onxol,Paclitaxel, (4 alpha)-Isomer,Paxene,Praxel,Taxol,Taxol A,7 epi Taxol,NSC 125973,NSC125973,Taxol, Bris

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