Skip Navigation



Carcinogenesis Advance Access published online on January 20, 2005
Carcinogenesis, doi:10.1093/carcin/bgi015
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/4/803    most recent
bgi015v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Wen, X.
Right arrow Articles by Walle, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wen, X.
Right arrow Articles by Walle, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Oxford University Press
Received October 6, 2004
Revised December 3, 2004
Accepted December 27, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

5,7-dimethoxyflavone down-regulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cells

Xia Wen 1, U. Kristina Walle 1, and Thomas Walle 1*

1 Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina

* To whom correspondence should be addressed.
Thomas Walle, E-mail: wallet{at}musc.edu


  Abstract

The objective of this study was to examine the ability of dietary polyphenols to inhibit cytochrome P450 (CYP) 1A1 expression and activity and benzo[a]pyrene (BaP) DNA binding, with the main emphasis on prevention of chemical-induced hepatic carcinogenesis. For this purpose we used Hep G2 cells, a good model of the normal human hepatocyte for CYP1A1 cell signaling. First, when these cells were exposed to a low concentration (1 µM) of BaP, DNA binding occurred, which dramatically increased after 6 hr of treatment. BaP also dramatically induced CYP1A1 activity, protein expression, and mRNA levels, likely the reason for the marked increase in DNA binding. Second, we screened 25 polyphenols with highly varying chemical structures for maximum ability to inhibit CYP1A1 activity in the Hep G2 cells. Highly variable responses were obtained, ranging from a 10-fold induction by some polyphenols to almost complete inhibition, in particular by 5,7-dimethoxyflavone (DMF), a flavonoid found in some tropical plants. Third, we examined the ability of DMF to inhibit DNA binding of BaP and the mechanisms involved. DMF (2 to 20 µM) inhibited BaP-induced DNA binding. DMF also inhibited BaP-induced CYP1A1 activity, CYP1A1 protein expression and mRNA levels. Moreover, DMF directly inhibited the catalytic activity of recombinant CYP1A1 with an IC50 of 0.8 µM. In conclusion, DMF was a highly potent inhibitor of BaP-induced DNA binding and CYP1A1 protein expression and activity in the Hep G2 cells. These properties may make DMF an effective chemoprotectant in chemical-induced liver cancer.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
C. J. MacDonald, R. Y. S. Cheng, D. D. Roberts, D. A. Wink, and G. C. Yeh
Modulation of Carcinogen Metabolism by Nitric Oxide-Aspirin 2 Is Associated with Suppression of DNA Damage and DNA Adduct Formation
J. Biol. Chem., August 14, 2009; 284(33): 22099 - 22107.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
U. K. Walle and T. Walle
Bioavailable Flavonoids: Cytochrome P450-Mediated Metabolism of Methoxyflavones
Drug Metab. Dispos., November 1, 2007; 35(11): 1985 - 1989.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
P. Sienkiewicz, H. P. Ciolino, B. J. Leslie, P. J. Hergenrother, K. Singletary, and G. C. Yeh
A novel synthetic analogue of a constituent of Isodon excisus inhibits transcription of CYP1A1, -1A2 and -1B1 by preventing activation of the aryl hydrocarbon receptor
Carcinogenesis, May 1, 2007; 28(5): 1052 - 1057.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
X. Wen and T. Walle
Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability
Drug Metab. Dispos., October 1, 2006; 34(10): 1786 - 1792.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
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]

Home page
 Drug Metab. Dispos.Home page
T. Walle, U. K. Walle, D. Sedmera, and M. Klausner
BENZO[A]PYRENE-INDUCED ORAL CARCINOGENESIS AND CHEMOPREVENTION: STUDIES IN BIOENGINEERED HUMAN TISSUE
Drug Metab. Dispos., March 1, 2006; 34(3): 346 - 350.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
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]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.