The Role of AHR in Breast Cancer Development
Abstract
The study described herein was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects growth of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen- responsive transcription factor implicated in mammary tumor initiation and growth control. Our results indicated that breast cancer Hs578T cells expressed high levels of constitutively active AhR. Constitutive and environmental chemical-inducible AhR activity was profoundly suppressed by galangin as was cell growth. However, the failure of a-naphthoflavone or FhAhRR transfection to block growth indicated that galangin- mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell growth at therapeutically relevant doses. Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth, likely through the nearly total elimination of cyclin D3. The results suggest that this non-toxic bioflavonoid may be useful as a chemotherapeutic, particularly in combination with agents which target other components of tumor cell cycle and in situations where estrogen receptor-specific therapeutics are ineffective.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA442985
Entities
People
- Xinhai Yang
Organizations
- Boston University