Combinatorial Withaferin A and Sulforaphane and Their Potential Roles in Breast Cancer Prevention and Therapy

摘要

Cancer is a leading cause of death worldwide and is a devastating disease. Breast cancer is of particular interest because it is a major cause of cancer-related fatality in women in the United States. To date, more than 40,000 women are expected to die due to breast cancer and more than 200,000 will be diagnosed every year. Despite numerous advancements in the field, breast cancer remedies can be harsh and while life may be prolonged, the quality of life may decrease. This being said, preventive measures and less harsh treatment options are needed to help eliminate breast cancer as a life threatening disease. This project explores the roles of combinatorial dietary compounds sulforaphane (SFN) and withaferin A (WA) in an effort to elucidate the mechanisms responsible for their efficacy in breast cancer cell death. We provide preliminary evidence that the use of these two compounds in conjunction may serve as ideal candidates for further study with regard to adjuvant therapy and secondary prevention of breast cancer. Our results show that combinatorial WA and SFN causes significant decreases in breast cancer cell viability and promotes apoptosis in two breast cancer cell lines. We further show that epigenetic modifiers are regulated by these compounds. In addition, we report that tumor suppressor genes are modulated and the genes associated with cell cycle progression are also impeded in response to these treatments. We attribute this regulation of the tumor suppressor genes studied in this project to changes in the epigenome induced by combinatorial WA and SFN.