Cancer Res. 2001 May 15;61(10):3919-24.  

Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of
cytochromes P50 1A1, 1A2, and 1B1.

MacDonald CJ, Ciolino HP, Yeh GC.

Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Division
of Basic Sciences, National Cancer Institute-Frederick, National Institutes of
Health, Frederick, MD 21702-1201, USA.

The phytochemical dibenzoylmethane (DBM) has been shown to prevent polycyclic
aromatic hydrocarbon (PAH)-induced tumorigenesis in rodents. However, the
biochemical basis of this activity is unclear. We have therefore investigated
the effects of DBM on the activity and expression of carcinogen-activating
enzymes, the cytochromes P450 (CYP) 1A1, 1A2, and 1B1. Oral administration of
DBM to female Sprague Dawley rats inhibited the increase in hepatic enzyme
activity and mRNA levels of CYP1A1, 1A2, and 1B1 caused by the PAH
7,12-dimethylbenz[a]anthracene (DMBA). However, DBM administration alone caused
an increase in both activity and expression in the liver, albeit to levels much
lower than that induced by DMBA. To characterize the molecular mechanisms
involved in this dual action of DBM, we examined the effects of DBM in vitro. In
HepG2 human hepatoma cells, DBM inhibited DMBA- and
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced enzyme activity and CYP1A1,
1A2, and 1B1 mRNA levels, whereas DBM itself induced activity and mRNA
expression. Modulation of CYP1A1 expression by DBM occurred at the
transcriptional level, as transient transfection assays demonstrated. Because
the transcription of CYP1A1 is regulated by the aryl hydrocarbon receptor (AhR),
we investigated the effect of DBM on AhR activation. DBM inhibited TCCD-induced
DNA-binding of the AhR to the xenobiotic-responsive element (XRE) of CYP1A1 as
measured by electrophoretic mobility shift assay. These data suggest that the
chemopreventive activity of DBM results from its ability to affect Phase 1
enzyme expression by modulation of AhR function.

PMID: 11358806 [PubMed - indexed for MEDLINE]