Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers.
Cell-based models have been used extensively in screening novel bioactive chemical entities. In this study, seven well-established mammalian cell lines, which have different origins, were utilized to compare their responses to the treatments of three detoxifying enzyme inducers, tert-butylhydroquinone (tBHQ), beta-naphthoflavone (beta-NF), and sulforaphane (SUL), which are potential chemopreventive compounds. The enzymatic activities of glutathione s-transferase (GST), NAD(P)H:quinone oxidoreductase (QR), aldehyde reductase (AR), and glutathione reductase (GR) were measured by kinetics methods using UV-Vis spectroscopy, and analyzed statistically by Student's t-test. Among these mammalian cell lines, the mouse hepatoma Hepa1c1c7 cells were the most robust and sensitive cells, which had higher basal as well as upregulated enzymatic activities. In human cell lines, the prostate LNCaP and hepatic HepG2 cells were also very responsive to the inducers. The results suggested that different cell lines responded differently to individual detoxifying gene inducer, and the selection of appropriate cell line is important for screening potential chemopreventive agents.
Jiang
Zhi-Qiang
ZQ
Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.
Chen
Chi
C
Yang
Bo
B
Hebbar
Vidya
V
Kong
A-N Tony
AN
D000449:Aldehyde Reductase / Q000096:biosynthesis; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D018890:Chemoprevention; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005980:Glutathione Reductase / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D008658:Inactivation, Metabolic / Q000502:physiology; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D019324:beta-Naphthoflavone; C018855:2-tert-butylhydroquinone; D010088:Oxidoreductases; D000449:Aldehyde Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D005982:Glutathione Transferase; C016766:sulforaphane