Flavone antagonists bind competitively with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) to the aryl hydrocarbon receptor but inhibit nuclear uptake and transformation

Molecular Pharmacology

Volumn 55, Issue 4, 1999, Pages 716-725

  Henry, Ellen C ^a,c   Kende, Andrew S ^a   Rucci, George ^a   Totleben, Michael J ^a   Willey, J Jeffrey ^a   Dertinger, Stephen D ^a   Pollenz, Richard S ^b   Jones, Jeffrey P ^a   Gasiewicz, Thomas A ^a  

^a UNIVERSITY OF ROCHESTER   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; 3' METHOXY 4' AZIDOFLAVONE; 3' METHOXY 4' NITROFLAVONE; AROMATIC HYDROCARBON RECEPTOR; FLAVONE DERIVATIVE; HEAT SHOCK PROTEIN 90; LUCIFERASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; DRUG RECEPTOR BINDING; ELECTROPHORETIC MOBILITY; HEPATOMA CELL; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; LIGAND BINDING; LIVER CYTOSOL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RAT; RECEPTOR DOWN REGULATION;

ANIMALS; BINDING SITES; CARCINOMA, HEPATOCELLULAR; CYTOSOL; DOWN-REGULATION; FLAVONOIDS; LIGANDS; LIVER; MALE; MICE; PROTEIN CONFORMATION; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ARYL HYDROCARBON; STRUCTURE-ACTIVITY RELATIONSHIP; SUBCELLULAR FRACTIONS; TETRACHLORODIBENZODIOXIN; TRANSCRIPTION, GENETIC; TUMOR CELLS, CULTURED;

EID: 0032948743     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (39)

1. Bjeldanes LF, Kim J-Y, Grose KR, Bartholomew JC and Bradfield CA (1991) Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: Comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci USA 88:9543-9547.
2. Bock KW (1993) Aryl hydrocarbon or dioxin receptor: biologic and toxic responses. Rev Physiol Biochem Pharmacol 125:2-41.
3. Carver LA and Bradfield CA (1997) Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. J Biol Chem 272: 11452-11456.
4. Cho SJ and Tropsha A (1995) Cross-validated R2-guided region selection for comparative molecular field analysis: a simple method to achieve consistent results. J Med Chem 38:1060-1066.
5. Ciolino HP, Wang TTY and Yen GC (1998) Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 IA1 activity. Cancer Res 58:2754-2760.
6. Cramer RD, Patterson DE and Bunce JD (1988) Comparative molecular field analysis (CoMFA). I. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959-5967.
7. Cunningham BDM, Threadgill MD, Groundwater PW, Dale IL and Hickman JA (1992) Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases. Anticancer Drug Des 7:365-384.
8. Fernandez N, Roy M and Lesca P (1988) Binding characteristics of Ah receptors from rats and mice before and after separation from hepatic cytosols. 7-Hydroxyellipticine as a competitive antagonist of cytochrome P-450 induction. Eur J Biochem 172:585-592.
9. Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SST, Kimura S, Nebert DW, Rudikoff S, Ward JM and Gonzalez FJ (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268:722-726.
10. Gasiewicz TA and Bauman PA (1987) Heterogeneity of the rat hepatic Ah receptor and evidence for transformation in vitro and in vivo. J Biol Chem 262:2116-2120.
11. Gasiewicz TA, Rende AS, Rucci G, Whitney B and Willey JJ (1996) Analysis of structural requirements for Ah receptor antagonist activity: ellipticines, flavones, and related compounds. Biochem Pharmacol 52:1787-1803.
12. Gasiewicz TA and Neal RA (1982) The examination and quantitation of tissue cytosolic receptors for 2,3,7,8-tetrachlorodibenzo-p-dioxin using hydroxylapatite. Anal Biochem 124:1-11.
13. Gasiewicz TA, Rucci G, Henry E and Baggs RB (1986) Changes in hamster hepatic cytochrome P-450, ethoxycoumarin O-deethylase, and reduced NAD(P):menadione oxidoreductase following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Partial dissociation of temporal and dose-response relationships from elicited toxicity. Biochem Pharmacol 35:2737-2742.
14. Gillner M, Bergman J, Cambillau C, Alexandersson M, Fernstrom B and Gustafsson J-A (1993) Interactions of indolo[3,2-b]carbazoles and related polycyclic aromatic hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. Mol Pharmacol 44:336-345.
15. Gillner M, Bergman J, Cambillau C, Fernstrom B and Gustafsson J-A (1985) Interactions of indoles with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. Mol Pharmacol 28:357-363.
16. Hankinson O (1995) The aryl hydrocarbon receptor complex. Ann Rev Pharmacol Toxicol 35:307-340.
17. Harris M, Zacharewski T, Astroff B and Safe S (1989) Partial antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated induction of aryl hydrocarbon hydroxylase by 6-methyl-1,3,8-trichlorodibenzofuran: mechanistic studies. Mol Pharmacol 35: 729-735.
18. Holmes JL and Pollenz RS (1997) Determination of aryl hydrocarbon receptor nuclear translocator protein concentration and subcellular localization in hepatic and nonhepatic cell culture lines: development of quantitative western blotting protocols for calculation of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclar translocator protein in total cell lysates. Mol Pharmacol 52:202-211.
19. Jones JP, He MX, Trager WF and Rettie AE (1996) Three-dimensional quantitative structure-activity relationship for inhibitors of cytochrome P4502C9. Drug Metab Dispos 24:1-6.
20. Kurl RN, DePetrillo PB and Olnes MJ (1993) Inhibition of Ah (dioxin) receptor transformation by 9-hydroxy ellipticine: involvement of protein kinase C? Biochem Pharmacol 46:1425-1433.
21. Liu H, Santostefano M, Lu Y and Safe S (1993) 6-Substituted 3,4-benzocoumarins: A new structural class of inducers and inhibitors of CYP1A1-dependent activity. Arch Biochem Biophys 306:223-231.
22. Lu Y-F, Santostefano M, Cunningham BDM, Threadgill MD and Safe S (1995) Identification of 3′-methoxy-4′-nitroflavone as a pure aryl hydrocarbon (Ah) receptor antagonist and evidence for more than one form of the nuclear Ah receptor in MCF-7 human breast cancer cells. Arch Biochem Biophys 310:470-477.
23. Lu Y-F, Santostefano M, Cunningham BDM, Threadgill MD and Safe S (1996) Substituted flavones as aryl hydrocarbon (Ah) receptor agonists and antagonists. Biochem Pharmacol 51:1077-1087.
24. Lusska A, Shen E and Whitlock JP, Jr (1992) Protein-DNA interactions at a dioxin-responsive enhancer: Analysis of six bona fide DNA-binding sites for the liganded Ah receptor. J Biol Chem 268:6575-6580.
25. Ma Q and Whitlock JP, Jr (1997) A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem 272:8878-8884.
26. Manon MJ and Gasiewicz TA (1992) Chelatable metal ions are not required for aryl hydrocarbon receptor transformation to a DNA binding form: Phenanthrolines are possible competitive antagonists of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Biochem Biophys 297:1-8.
27. McDonnell DP, Clemm DL and Imhof MO (1994) Definition of the cellular mechanisms which distinguish between hormone and antihormone activated steroid receptors. Sem Cancer Biol 5:327-336.
28. Perdew GH, Abbott B and Stanker LH (1995) Production and characterization of monoclonal antibodies directed against the Ah receptor. Hybridoma 14:279-283.
29. Poland A, Glover E and Bradfield CA (1991) Characterization of polyclonal antibodies to the Ah receptor prepared by immunization with a synthetic peptide hapten. Mol Pharmacol 39:20-26.
30. Pollenz RS (1996) The aryl-hydrocarbon receptor, but not the aryl-hydrocarbon receptor nuclear translocator protein, is rapidly depleted in hepatic and nonhepatic culture cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol Pharmacol 49:391-398.
31. Pollenz RS, Sattler CA and Poland A (1994) The aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator protein show distinct subcellular localizations in Hepa 1c1c7 cells by immunofluorescence microscopy. Mol Pharmacol 45:428-438.
32. Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, Agurell E and Grafstom AK (1987) Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J Biol Chem 262:15422-15427.
33. Reiners JJ, Jr., Lee J-Y, Clift RE, Dudley DT and Myrand SP (1998) PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase. Mol Pharmacol 53:438-445.
34. Safe S (1990) Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol 21:51-88.
35. Schmidt JV, Su GH-T, Reddy JK, Simon MC and Bradfield CA (1996) Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA 93:6731-6736.
36. Schrenk D, Riebniger D, Till M, Vetter S and Fiedler H-P (1997) Tryptanthrins: A novel class of agonists of the aryl hydrocarbon receptor. Biochem Pharmacol 54:165-171.
37. Waddell WJ (1956) A simple ultraviolet spectrophotometric method for the determination of protein. J Lab Clin Med 48:311-314.
38. Waller CL and McKinney JD (1995) Three-dimensional quantitative structure-activity relationships of dioxins and dioxin-like compounds: Model validation and Ah receptor characterization. Chem Res Toxicol 8:847-858.
39. Whitlock JP, Jr (1990) Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. Ann Rev Pharmacol Toxicol 30:251-277.