Plant Estrogens: Effects on Cell Cycle Progression in Breast Cancer Cells
Abstract
Epidemiological studies suggest that consumption of soy phytoestrgoens, such as genistein, is associated with a decrease risk of breast cancer. Genistein has been shown to exert chemopreventive and antiproliferative in animal models of cancer and breast cancer cells respectively. Accumulating evidence suggest that genistein is oxidatively metabolized by the cytochrome P45O (CYP45O) family of enzymes, and that its metabolism is specific to breast cancer cells but not nontransformed breast epithelial cells. We investigated the cellular association and effects of metabolism of genistein by CYP45O in T47D breast cancer cells and MCFlOA breast epithelial cells. These studies show that genistein exerts distinct effects on cell cycle progression that is due to its preferential cellular uptake and extent of its metabolism in T47D cells but not MCFlOA cells. Few studies describe the cell cycle effects of genistein on nontumorigenic breast epithelial cells. We compared the effects of genistein on cell proliferation, cell cycle progression, cell cycle checkpoints in T47D breast cancer cells and MCFlOA nontumorigenic breast epithelial cells. In T47D breast cancer cells, genistein caused G2 arrest with inhibition of cyclin dependent kinase activity at 25 MicronM or higher with concomitant upregulation of cyclin A and B. Upregulation of cyclin dependent kinase inhibitors, p2l and p27 expressions were not sufficient to inhibit kinase activity. Collectively, these. data show that genistein the mechanism for cell cycle arrest involves deregulation of cdc-2/cyclin B complex or cyclin Bicyclin B kinase complex through CDK inhibition. In contrast, there was less G2 arrest in MCFlOA nontumorigenic breast epithelial cells with increases in kinase activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418662
Entities
People
- Enrique Cadenas
Organizations
- University of Southern California