Molecular Basis of Anticancer Activity by the Flavanoid Fisetin

Breast cancer continues to be the most common cancer in Canadian women. The chance that a woman in Canada will be diagnosed with breast cancer is about 1 in 9 and the chance that a woman will die of this disease is 1 in 28. In addition, treatment can seriously impact on quality of life. Surgery may be complicated by arm swelling and nerve injury, and the need to remove the breast can cause emotional stress in some patients. If the cancer cannot be controlled with surgery, chemotherapy needs to be used. These anticancer drugs are also harmful to normal cells and the cancer cells can become resistant to treatment. Therefore, there is a need to Identify new and more effective drugs that can prevent cancer from developing, are able to kill chemotherapy-resistant cancer cells, and are less toxic to normal cells. It is well known that certain fruits and vegetables, and their extracts, are able to kill cancer cells without harming normal cells. Fisetin is a plant extract that comes from grapes and apples, and is a potent killer of prostate cancer cells. This research project will, for the first time, explore the anticancer activity of fisetin in human breast cancer. Preliminary results show that fisetin causes death in cultures of human breast cancer cells. The mechanism of breast cancer cell killing by fisetin will also be determined. Finally, the anticancer activity of fisetin will be confirmed in a mouse model of breast cancer. The results of this study may lead to a fisetin-based therapy for breast cancer that is more effective and has less adverse side effects than conventional chemotherapy.