Date of Award
Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha mangostin has potential to be an effective p53 activator in which the small molecule disrupts the binding of p53 to MDMD, a negative regulator, causing the p53 cascade which results in cell cycle arrest for low level stressors. This protects the cells from Paclitaxel, a chemotherapy that only kills actively dividing cells. When MCF10A wild type cells were cotreated with alpha mangostin and paclitaxel, they exhibited a protective effect. When MCF10A P53 knockout cells were treated with alpha mangostin, they appeared to decrease cell viability. Therefore, this treatment stands as a potential chemoprotectant that warrants further study.
Van Oost, Vanessa, "Study of alpha mangostin as a chemoprotective agent for breast cancer via activation of the p53 pathway" (2018). Pence-Boyce STEM Student Scholarship. 5.