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 formafion and/or growth of mammary tumors in redents. In this study, we have investigated the aryl hydrocarbon receptor (MIR) agonist activity and inhibitory AliR-estrogen receptor crosstalk induced by the following methyl-substituted DIMs: 1,1'-dimethyl-, 2,2'-dimethyl-, 5,5'-dimethyl-, 6,6'-dimethyl-, and 7,7'-dimethylDlM and 1,1',2,2'-tetramethy1DIM. The six compounds exhibited minimal to non-detectable AlIR 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/kW every second day fX10). l,l'DimethylDIM, 5,5'-dimethylDlM 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 (SAliRMs) with potential for clinical treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385387
Entities
People
- Jeong-eun Lee
Organizations
- Texas A&M University