Grant: Master's Award: Canada Graduate Scholarships

Cancer is among the leading causes of death worldwide. Roughly 40% of Canadians will be diagnosed with the disease during their lifetime, based on a 2009 projection by the Canadian Cancer Society. Although tools have been developed to fight cancer very effectively in some cases, cancer cells often exhibit an ability to evade death by both conventional and newer chemotherapeutic agents. Multidrug Resistance Protein 1 (MRP1) is a protein "pump" that normally serves a protective role by exporting toxic molecules out of cells. By making more of the MRP1 protein, cancer cells use MRP1 to export anti-cancer drugs and thus avoid death. Such MRP1 positive cancer cells are said to be 'multidrug resistant'. Bioflavonoids (naturally occurring compounds abundant in fruits and vegetables) are thought to have many health benefits. Several bioflavonoids cause MRP1 to export high levels of the anti-oxidant glutathione (GSH) from cells. GSH neutralizes many toxic metabolites including free radicals, and thus depletion of GSH results in a buildup of free-radicals that can kill the cancer cell. How bioflavonoids cause the export of GSH by MRP1, is poorly understood at a molecular level. The first step in understanding how these bioflavonoids might be better exploited for their ability to kill resistant cancer cells is understanding how all three players (bioflavonoids, GSH, and MRP1) physically interact with each other. Thus, the goal of this research project is to identify the specific region (or regions) on the MRP1 protein that interacts with these molecules. This will give insight into how better to use these bioflavonoids to treat multidrug resistant cancers.