Aryl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs
Abstract
Diindolylmethane (DIM) is formed by acid catalyzed dimerization of indole-3-carbinol, and both compounds inhibit formation and/or growth of mammary tumors in rodents. In this study, we have investigated the aryl hydrocarbon receptor (AhR) agonist activity and inhibitory AhR-estrogen receptor crosstalk induced by the following methyl-substituted DIMs: 1,11-dimethyl-; 2,2'- dimethyl-; 5,5' -dimethyl; 6,6' -dimethyl-; and 7,7' -dimethylDIM; and 1,1' ,2,2' -tetramethylDIM. The six compounds exhibited minimal to non-detectable AhR agonist or antagonist activities associated with CYPlAl induction. In contrast, the methyl-substituted DIMs inhibited estrogen-induced T47D human breast cancer cell growth. The antitumorigenic activity of these compounds was examined in 7,l2-dimethylbenzAanthracene-induced rat mammary tumor model in which the DIM analogs were orally administered (by gavage in corn oil) at a dose of 1 mg/kg/every second day (Xl0) . l,l'-DimethylDIM, 5,5'-dimethylDIM and l,l',2,2'-tetramethylDIM significantly inhibited mammary tumor growth, and this was not accompanied by changes in organ/body weights or histopathology. These studies demonstrate that methyl-substituted DIMs are selective AhR modulators (SAhRMs) with potential for clinical treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA400528
Entities
People
- Jeong-eun Lee
Organizations
- Texas A&M University