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Comparative Analysis and Functional Characterization of HC-AFW1 Hepatocarcinoma Cells: Cytochrome P450 Expression and Induction by Nuclear Receptor Agonists.
Braeuning, Albert; Thomas, Maria; Hofmann, Ute; Vetter, Silvia; Zeller, Eva; Petzuch, Barbara; Johänning, Janina; Schroth, Werner; Weiss, Thomas S; Zanger, Ulrich M; Schwarz, Michael.
Afiliación
  • Braeuning A; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Thomas M; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Hofmann U; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Vetter S; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Zeller E; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Petzuch B; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Johänning J; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Schroth W; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Weiss TS; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Zanger UM; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
  • Schwarz M; Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (A.B.); Dr.-Margarethe-Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany (M.T., U.H., J.J., W.S., U.M.Z.); Department of Toxicology, Institute of Experimental a
Drug Metab Dispos ; 43(11): 1781-7, 2015 Nov.
Article en En | MEDLINE | ID: mdl-26310804
Enzymatic conversion of most xenobiotic compounds is accomplished by hepatocytes in the liver, which are also an important target for the manifestation of the toxic effects of foreign compounds. Most cell lines derived from hepatocytes lack important toxifying or detoxifying enzymes or are defective in signaling pathways that regulate expression and activity of these enzymes. On the other hand, the use of primary human hepatocytes is complicated by scarce availability of cells and high interdonor variability. Thus, analyses of drug metabolism and hepatotoxicity in vitro are a difficult task. The cell line HC-AFW1 was isolated from a pediatric hepatocellular carcinoma and so far has been used for tumorigenicity and chemotherapy resistance studies. Here, a comprehensive characterization of xenobiotic metabolism in HC-AFW1 cells is presented along with studies on the functionality of the most important transcriptional regulators of drug-metabolizing enzymes. Results from HC-AFW1 cells were compared with commercially available HepaRG cells and cultured primary human hepatocytes. Data show that the nuclear receptors and xenosensors AHR (aryl hydrocarbon receptor), CAR (constitutive androstane receptor), PXR (pregnane-X-receptor), NRF2 [nuclear factor (erythroid-derived 2)-like 2], and PPARα (peroxisome proliferator-activated receptor α) are functional in HC-AFW1 cells, comparable to HepaRG and primary cells. HC-AFW1 cells possess considerable activities of different cytochrome P450 enzymes, which, however, are lower than corresponding enzyme activities in HepaRG cells or primary hepatocytes. In summary, HC-AFW1 are a new promising tool for studying the mechanisms of the regulation of drug metabolism in human liver cells in vitro.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Enzimológica de la Expresión Génica / Receptores Citoplasmáticos y Nucleares / Carcinoma Hepatocelular / Sistema Enzimático del Citocromo P-450 / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Enzimológica de la Expresión Génica / Receptores Citoplasmáticos y Nucleares / Carcinoma Hepatocelular / Sistema Enzimático del Citocromo P-450 / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos