Hormone replacement therapy is an effective means to prevent post-menopausal degenerative diseases but has been reported to increase breast cancer risk. Ôamoxifen (Novaldex®) and raloxifene (Evista®) are known to act as estrogen antagonists in the breast and as estrogens in non-reproductive estradiol-target tissues. However, their potential to substitute for estrogens in preventing degenerative diseases is equivocal. We used genetically engineered cell lines of breast, uterine, kidney and neuronal origin to assess the estrogen agonist and antagonist properties of natural and synthetic estrogen receptor modulators. We evaluated a series of new tamoxifen and raloxifene analogues, designed to provide for a higher stabilization of the antagonist conformation of the receptor, and found that some exhibit minimal uterotropic activity. We also evaluated deoxybenzoins, benzofurans and stilbenoids with established receptor-binding activity in order to spot those exhibiting selective cytostatic, cytotoxic and neuroprotective activity, respectively. The molecular determinants and mechanisms of action relating to the biological activity of the above estrogen receptor modulators will be discussed.
Speaker: Michael N Alexis, PhD.
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation.
Time: Monday, 10 April 2006, 13:00