| Abstract | Today over 14 million patients fight some form of cancer or another (World Health Organization). In females, breast cancer is the most prevalent cancer with nearly 1.5 million cases diagnosed and 500,000 deaths every year. A characteristic feature of some breast cancer cells is that they over-express the estrogen receptor (ER). Upon binding to its ligand, estradiol, the cytoplasmic estrogen receptor translocates into the nucleus, binds to the nuclear DNA and regulates the expression of various genes. We have designed a DNA methylating agent, called Melex, which specifically enters ER expressing breast cancer cells. We used carbon linkers of variable lengths to conjugate Melex to estradiol (Est-Melex). This, based on the model described above, will allow Melex to be specifically taken up by ER+ breast cancer cells and brought in close proximity to the cancer cell's nuclear DNA which the drug can now methylate and cause cell death. Our collaborators at the University of North Carolina, Wilmington, designed three variants of this drug, each differing only in the number of carbons in the backbone of the linker. The goal of our project is to find the variant that is most efficient in killing ER+ breast cancer cells. Additionally, if we do observe cell death, we wish to find the mode of cell death. Identification of such a drug that is efficient and specific in killing ER over expression in breast cancer cells will give us a new weapon that can be used in our fight against breast cancer. |
