Molecular Mechanism of Action of Genistein and Related Phytoestrogens in Estrogen Receptor Dependent & Independent Growth of Breast Cancer Cells.
Abstract
During the first year of my pre-doctoral fellowship, I have demonstrated that genistein binds weakly to the estrogen receptor (ER) with an IC50 value of 900 nM (task 1). Quercetin and genistein also bind to the type-II estrogen binding sites, and exert cell growth inhibition in MCF-7 and MDA-MB-468 cells (task 2). In circular dichroism studies, decreased intensity of the spectra leading to a random recombinant ER structure was observed with genistein (task 3). Genistein (10 Microns) stimulated the growth of MCF-7 cells at 24 h, however, by 72 h, it was growth inhibitory at all doses (task 5). A major cell cycle block at G2/M phase was observed with genistein treatment and was accompanied by alterations in cyclin B1 levels (tasks 7 and 8). In addition, we show that cell growth inhibition by genistein and quercetin is associated with decreased polyamine levels. Our results provide insights into the ER-dependent and -independent mechanisms of action of genistein in breast cancer cell growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA354079
Entities
People
- Srivani Balabhadrapathruni