An Investigation of the Anti-Cancer Effects of Apple Flavonoids Fraction 4 on Breast Cancer Cells

Abstract

Cancer remains to be the one of the leading causes of death in Canada and the United States. In Canadian and American women, breast cancer is the second leading cause of cancer-related deaths behind lung cancer, despite large advancements in our understanding of the disease. One major reason for this is the lack of novel therapeutics that can selectively target triple-negative breast cancers. This project attempts to solve this problem using a collection of phytochemicals found in the peels of Northern Spy apples, called AF4. Using a variety of flow cytometry techniques and western blotting, apple flavonoids fraction (AF4) was found to kill triple-negative breast cancer cells while being non-toxic to healthy epithelial cells. This cell death occurred without the cleavage of caspases or poly (ADP-ribose) polymerase 1 (PARP1) and was determined to be at least in part dependent on reactive oxygen species (ROS). In addition, AF4 inhibited the proliferation of triple-negative breast cancer cells via G1 cell cycle arrest. AF4 seems to inhibit the phosphorylation of Akt via a ROS-dependent mechanism; however, inhibition of the PI3K/Akt pathway does not seem to be responsible for decreased proliferation. In addition, AF4 altered the expression of enzymes involved in epigenetic modulation in both triple-negative breast cancer and epithelial cell lines. The findings of this project highlight the potential of AF4 as a possible selective triple-negative breast cancer treatment.