Toxicological Sciences 58, 235-242 (2000)
Copyright © 2000 by the Society of Toxicology
Biotransformation and Toxicokinetics |
3',4'-Dimethoxyflavone as an Aryl Hydrocarbon Receptor Antagonist in Human Breast Cancer Cells
Department of Veterinary Physiology & Pharmacology, Texas A&M University, 4466 TAMU, College Station, Texas 77843
Treatment of MCF-7 and T47D human breast cancer cells with 3',4'-dimethoxyflavone (3',4'-DMF) alone did not induce CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity or reporter gene activity in cells transfected with an aryl hydrocarbon (Ah)-responsive construct (pRNH11c). In contrast, 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced up to a 50- to 80-fold increase in EROD and reporter gene activity in MCF-7 and T47D cells. In cells cotreated with 1 nM TCDD plus 0.1–10 µM 3',4'-DMF, there was a concentration-dependent decrease in the TCDD-induced responses, with 100% inhibition observed at the 10 µM concentration. Gel mobility shift assays using rat liver cytosol and breast cancer cell nuclear extracts showed that 3',4'-DMF alone did not transform the AhR to its nuclear binding form, but inhibited TCDD-induced AhR transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF-7 and T47D cells. TCDD also inhibited estrogen-induced transactivation in MCF-7 cells, and this response was also blocked by 3',4'-DMF, confirming the AhR antagonist activity of this compound in breast cancer cells.
Key Words: AhR; antagonist; breast cancer cells; 3',4'-dimethoxyflavone.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Chang, K.-w. Peng, I. Kastrati, C. R. Overk, Z.-H. Qin, P. Yao, J. L. Bolton, and G. R. J. Thatcher Activation of Estrogen Receptor-Mediated Gene Transcription by the Equine Estrogen Metabolite, 4-Methoxyequilenin, in Human Breast Cancer Cells Endocrinology, October 1, 2007; 148(10): 4793 - 4802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Okey An Aryl Hydrocarbon Receptor Odyssey to the Shores of Toxicology: The Deichmann Lecture, International Congress of Toxicology-XI Toxicol. Sci., July 1, 2007; 98(1): 5 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Tsuji and T. Walle Inhibition of benzo[a]pyrene-activating enzymes and DNA binding in human bronchial epithelial BEAS-2B cells by methoxylated flavonoids Carcinogenesis, August 1, 2006; 27(8): 1579 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. E. Lin, S.-C. Chien, P.-C. Hsu, and L.-A. Li Mechanistic Study of Polychlorinated Biphenyl 126-Induced CYP11B1 and CYP11B2 Up-Regulation Endocrinology, March 1, 2006; 147(3): 1536 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Totta, F. Acconcia, F. Virgili, A. Cassidy, P. D. Weinberg, G. Rimbach, and M. Marino Daidzein-Sulfate Metabolites Affect Transcriptional and Antiproliferative Activities of Estrogen Receptor-{beta} in Cultured Human Cancer Cells J. Nutr., November 1, 2005; 135(11): 2687 - 2693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wen and T. Walle Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols Carcinogenesis, October 1, 2005; 26(10): 1774 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wen, U.K. Walle, and T. Walle 5,7-Dimethoxyflavone downregulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cells Carcinogenesis, April 1, 2005; 26(4): 803 - 809. [Abstract] [Full Text] [PDF]
|
|