| dc.description.abstract | Cancer cells are characterized by loss of regulation of the cell cycle that results in uncontrolled proliferation. To drive this high rate of cellular division, cancer cells have mutated to increase uptake of vitamins by increasing the number of vitamin receptors, including biotin receptors, on their surface. Due to this difference in expression of biotin receptor between cancer and normal cells, research focusing on the use of biotin-conjugated molecules has gained attention as a method for anticancer drug delivery. Another characteristic unique to certain cancer cells is that they exhibit dysregulation in normal cellular redox balance, such that certain redox reactions are favored that generate reactive oxygen species (ROS) and lead to oxidative stress. Many metal-based anticancer drugs have taken advantage of this feature of cancer cells in an attempt to increase the levels of ROS to the point that cell death occurs. Specifically, the iron atom of ferrocene has been shown to lead to the generation of damaging ROS upon oxidation from Fe2+ to Fe3+. This research project focuses on testing the cytotoxicity of a variety of biotin-ferrocene compounds on cancer (HeLa and MCF7) and non-cancer (293HEK) cell lines. The tested compounds have three main features: a biotin moiety, a ferrocene core, and a variable side-chain covalently bound to the ferrocene moiety. We hypothesize that the biotin-containing compounds will enter HeLa and MCF7 cells more efficiently than 293HEK cells, allowing for the ferrocene moiety to reduce oxygen, leading to increased ROS generation and, ultimately, cell death. Here, we demonstrate that ferrocene shows cytotoxicity specific to cancer cells. Three of the biotin-ferrocene compounds appear to be more toxic to cancer cells relative to non-cancer cells. Future studies are required to reveal how the differences in cytotoxicity are related to the differences in chemical moieties and exactly how these compounds cause specific cytotoxicity. | |
