The Efficacy of Poly(trolox ester) Antioxidant Therapy in Cancer Metastasis Inhibition

Circulating tumor cells that metastasize from a primary tumor are responsible for 90% of cancer-related deaths in the United States. These circulating tumor cells can adhere to the endothelial lining of the vascular system and extravasate to form deadly secondary tumors. Reactive oxygen species (ROS) are produced within the endothelial cells of the vasculature from shear stress of blood flow, but are balanced by natural occurring anti-oxidants. Loss of blood supply to endothelial cells from invasive primary tumor removal surgeries can cause an imbalance in the consumption and production of ROS causing oxidative stress and also upregulate cellular adhesion molecules. If circulating tumor cells are within the system while endothelial cells are experiencing oxidative stress, cancer cells may adhere to the endothelial lining more readily. Static studies were conducted on a monolayer of human umbilical vein endothelial cells (HUVECs) to investigate the role of oxidative stress and inflammation on cancer cell adhesion to endothelial cells. The HUVECs were exposed to factors related to the inflammatory response such as TNF-α and a hypoxanthine (HX)-xanthine oxidase (XO) reaction to simulate the conditions the endothelial cells experience during extensive surgeries. This project explains the correlation between the generation of ROS, the upregulation of cellular adhesion molecules, and the adhesion of breast cancer cells to a HUVEC monolayer. The studies were repeated using antioxidant nanoparticle treated HUVECs to determine the efficacy of Poly(trolox ester) antioxidant nanoparticles.