Dr. Gregory Long
Scholarship of Discovery
Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths each year 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 a very common 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 is an extract from a southeast Asian fruit, Garcinia mangostana. It has potential to be an effective p53 activator in which the small molecule disrupts the binding of p53 to MDM2, a negative regulator, inducing the p53 cascade which results in cell cycle arrest for low level stressors. This protects the cells from paclitaxel, a chemotherapy agent that only kills actively dividing cells. Here, we hypothesized that alpha mangostin protects wild-type, but not p53 (-/-), MCF10A breast cancer cells from the chemotherapeutic agent paclitaxel. When MCF10A wild-type cells were cotreated with alpha mangostin and paclitaxel, alpha mangostin exhibited a protective effect on the cells. However, when MCF10A P53 knockout cells were treated with alpha mangostin, cell viability decreased indicating a loss of protective effect in the p53 distressed cancer cells. These results further support treatments that target chemoprotection via p53 pathway in wild-type cells and the use of alpha mangostin warrants further study.
Van Oost, Vanessa, "Study of alpha mangostin as a chemoprotective agent for breast cancer via activation of the p53 pathway" (2019). Honors Program Projects. 105.
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