Grant: Travel Awards - Institute Community Support

Cancer is a major health concern and is one of the leading causes of death in Canada and worldwide. Although doxorubicin (Dox) is the most effective and commonly used anti-cancer drug, it has serious side effects on heart leading to heart failure. In an animal model, we have shown that Dox causes damage to the heart by increased production of harmful substances known as "reactive oxygen species" which results in a stressful condition known as "oxidative stress". Dox being widely used for treatment of various cancers, it is important to reduce its harmful effects on heart and preserve the heart functions. Treatment with Vitamin C (Vit C) has shown to decrease oxidative stress and cause overall improvement in survival of the heart cells. However, in order to exert its beneficial effects, Vit C has to be efficiently transported in the cells. Certain proteins, known as "Vit C transporter" carry Vit C inside the cells, treatment with Dox causes a decrease in these transporter protein. Low levels of cellular Vit C were seen in patients treated with Dox. However there is no information on how Dox affects transport of Vit C in heart cells. In my project, i propose that Dox causes an increase in oxidative stress and a decrease in Vit C transporter protein, whereas treatment with Vit C would counteract this effect and increase Vit C transporter protein and thereby increase cellular uptake of Vit C. Understanding the mechanism by which Vit C transport is affected will suggest ways to improve Vit C uptake in the heart cells and reduce the oxidative stress and damage associated with Dox. Beneficial effects of pretreatment with Vit C will be explored on Vit C transporters and thus the heart structure and function. Through the detailed knowledge of how Dox affects the inside of heart cell and how Vit C protects these cells, we can have improved management of heart function in cancer patients on chemotherapy.