Skip Navigation



Carcinogenesis Advance Access published online on September 28, 2006
Carcinogenesis, doi:10.1093/carcin/bgl169
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrowOA All Versions of this Article:
28/3/639    most recent
bgl169v1
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
Google Scholar
Right arrow Articles by Puppala, D.
Right arrow Articles by Swanson, H. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Puppala, D.
Right arrow Articles by Swanson, H. I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s)
Received February 15, 2006
Revised August 22, 2006
Accepted September 1, 2006

CANCER PREVENTION

Identification of kaempferol as an inhibitor of cigarette smoke induced activation of the aryl hydrocarbon receptor and cell transformation

D. Puppala 1, C. G. Gairola 2, and H. I. Swanson 1 *

1 Department of Molecular and Biomedical Pharmacology, MS 305 University of Kentucky Medical Center, KY 40536
2 Graduate Center for Toxicology, University of Kentucky Lexington, KY 40536

* To whom correspondence should be addressed.
H. I. Swanson, E-mail: hswan{at}uky.edu


  Abstract

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor which upon activation by its agonists, translocates into the nucleus and forms a dimer with ARNT (aryl hydrocarbon nuclear translocator). The AHR/ARNT dimer regulates the expression of its target genes by binding to DNA recognition elements termed dioxin responsive elements (DREs). Many AHR agonists, like the polyaromatic hydrocarbons and polyhalogenated hydrocarbons are known human carcinogens. Human exposure to these compounds is common due to their presence in air pollution and cigarette smoke. Interestingly, many dietary constituents that have chemo preventative properties have been found to also act as antagonists of the AHR pathway. Thus, a chemopreventive approach that may be effective in decreasing the incidences of many human cancers may involve a dietary regimen that includes a number of these naturally occurring AHR antagonists. With this idea in mind, we have assayed the ability of 15 flavonoids to inhibit AHR activated reporter activity and selected kaempferol for further analysis. Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA binding complex and upregulation of the AHR target gene, CYP1A1. Using an in vitro paradigm of events that are thought to occur during cigarette smoke-induced lung cancer, we found that kaempferol also inhibited the ability of cigarette smoke condensate to induce growth of immortalized lung epithelial (BEAS-2B) cells in soft agar. Taken together, these results illustrate the promise associated with the use of flavonoids that inhibit both AHR signaling and the carcinogenic actions of AHR agonists for chemopreventive purposes.


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




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.