Dhivyashree Senthil Murugan, “Biological Investigation of Phenylboronic Acid Nitrogen Mustards Induced Cell Death in Triple Negative Breast Cancer”
Mentors: Xiaohua Peng and Taufeeque Ali , Chemistry & Biochemistry
Poster #120

Triple Negative Breast Cancer (TNBC) tests negative for the presence of hormonal receptors such as progesterone and estrogen receptors and excess human epidermal growth factor (HER2 protein). TNBC is unaffected by hormonal treatments that target these three growth factors. After diagnosis, there is less time than other cancers to treat TNBC. These characteristics of TNBC results in having poorer prognosis among all types of breast cancer. Therefore, there is dire need for a better understanding of the cancer and of potential drugs. Based on previous research, we have concluded that two Phenylboronic acid nitrogen mustard prodrugs, namely, CWB-20I45 and FAN-NM-CH₃ are effective in reducing tumor sizes due to prodrugs’ enhanced activity in the presence of hydrogen peroxide (H₂O₂). Prodrugs are initially inactive that are then turned into an active compound upon metabolism. Inside cells, these prodrugs cause DNA cross-linking that ceases DNA replication and leads to apoptosis, making them superior to common chemotherapy drugs, i.e., chlorambucil and melphalan. Cancer cells have higher levels of reactive oxygen species (ROS) such as H₂O₂. The prodrugs are thus more selective to cancer cells and less toxic to normal cells. A series of in-vivo experiments determined that the prodrugs are safer in mice. To understand the drug’s mechanism inside cells, we investigated biological pathways by looking at protein expression levels, which vary in drug-treated cells. These proteins include tumor suppressor p53. This was done using RT-qPCR technique to amplify RNA upon extracting mRNA between cancerous cells that are untreated versus drug-treated.