| dc.description.abstract | Breast cancer (BC) is the second most commonly diagnosed cancer among American women after skin cancer. Traditional treatments of BC include surgery, radiation, and chemotherapy therapy; however, these treatments are non-specific and potentially kill peripheral, healthy cells. There emerges a need for more specific treatments, most notably to develop chemotherapy agents that target a unique feature of the cancer cells. Interestingly, 70% of BC cells upregulate estradiol-dependent pathway, a characteristic essential for rapid cell growth. Current BC drugs, such as Herceptin and Tamoxifen, have targeted this pathway to preferentially kill BC cells. However, most women relapse within 15 years due to drug-resistance. Thus, there is a need for new chemotherapeutic drugs. Our research group studies a novel estrogen-receptor targeting drug: Est-n-Melex. This compound has the Estradiol (Est) moiety linked to a DNA alkylating agent, Melex via a linker of varying length of methyl groups. We hypothesize that Est-n-Melex enters the cancer cells via an interaction between the Est moiety and the estrogen receptor alpha (ER-alpha). ER-alpha then dimerizes, enters the nucleus and binds to Estrogen Response Elements on the DNA. This movement positions the Melex moiety on the DNA and allows the transfer of a methyl group to the N-3 adenine on the DNA. In this project, we test the hypothesized mechanism of action of our compound. Since Est-n-Melex has a DNA methylation component (Melex) conjugated to estrogen, our hypothesis is that after the drug binds to the ER-alpha in the cytosol, it translocates to the nucleus, specifically methylates the N3-region of adenine bases, eventually triggering cell death. | |
