RT Journal Article
SR Electronic
T1 Comparative Analysis and Functional Characterization of HC-AFW1 Hepatocarcinoma Cells: Cytochrome P450 Expression and Induction by Nuclear Receptor Agonists
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1781
OP 1787
DO 10.1124/dmd.115.064667
VO 43
IS 11
A1 Albert Braeuning
A1 Maria Thomas
A1 Ute Hofmann
A1 Silvia Vetter
A1 Eva Zeller
A1 Barbara Petzuch
A1 Janina Johänning
A1 Werner Schroth
A1 Thomas S. Weiss
A1 Ulrich M. Zanger
A1 Michael Schwarz
YR 2015
UL http://dmd.aspetjournals.org/content/43/11/1781.abstract
AB 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.