The Effects of Fatty Acids on Retinoid Signaling in Human Mammary Epithelial Cells and Breast Cancer Cells
Abstract
Retinoic acid (RA) regulates the proliferation of a wide variety of cell types through the action of retinoic acid receptors. Phytanic acid (PA) and docosahexaenoic acid (DHA) are diet-derived fatty acids that bind to rexinoid X receptors (RXR). Therefore, we hypothesized that inhibitory effects on cell proliferation may be enhanced by the addition of PA and DHA to RA- treated cells. We demonstrate that 1) the combination of PA or DHA with RA resulted in enhanced growth arrest of estrogen receptor positive human breast cancer (HBC) cells; 2) PA and DHA induced growth arrest of estrogen receptor negative HBC cells; 3) synthetic RXR agonists induced growth inhibitory effects similar to PA and DHA in HBC cells; and 4) PA enhanced RA-induced expression of ribo mRNA in HBO cells and in murine embryonic stem cells. Our data indicate that PA and DHA may be useful adjuvant agents when retinoids are used to inhibit cell proliferation and/or to induce cell differentiation. Deciphering the effects of diet-derived RXR agonists may lead to new therapeutic and experimental uses of these agents in combination with retinoids.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA446736
Entities
People
- Lorraine J. Gudas
- Simne Langton
Organizations
- Cornell University