Grant: CIHR Fellowship

Nowadays, many patients can survive cancer thanks to advanced screening and therapy, but the anti-cancer therapy may have serious side effects that affect other parts of the body. For example, doxorubicin which is an effective anti-cancer drug may also cause heart failure. Unfortunately, the exact mechanism of doxorubicin-induced heart failure and the best prevention or treatment for this complication is still not known. Interestingly, resveratrol which is an active ingredient in red grapes and red wine is known to protect the heart from several forms of stress. Resveratrol protects the heart by increasing the activity of an enzyme that improves the energy utilization by the heart. This enzyme is called AMP-activated protein kinase. Therefore, we hypothesize that resveratrol will also protect against doxorubicin-induced heart failure by increasing the activity of this enzyme. In addition, we hypothesize that resveratrol will also enhance the anti-cancer effect of doxorubicin. In order to test these hypotheses, we will perform a series of experiments. First, we will examine the heart function in doxorubicin-treated mice treated with or without resveratrol to confirm the protective effect of resveratrol against doxorubicin-induced heart failure. Second, we will investigate the protective effect of resveratrol in mice that lack the AMP-activated protein kinase to know if the protective effect of resveratrol depends on this enzyme. Third, we will investigate if the administration of resveratrol will increase the anti-cancer effect of doxorubicin in mice with cancer. Together these experiments will help us understand the mechanism of doxorubicin-induced heart failure and to confirm that resveratrol is able to prevent it. This may allow us to use resveratrol in cancer patients to improve the benefit and reduce the risk of doxorubicin-based therapy.