Natural and Synthetic Alkaloids for Cancer Therapy

Cancer is a disease of uncontrolled cell growth and proliferation that is predicted to directly affect 1 in 3 Canadians. Standard chemotherapy that targets DNA or its replicative machinery effectively eradicates cancer cells, but also causes non-specific toxicity to healthy cells. Pancratistatin, a natural alkaloid isolated from Hymenocallis littoralis, was found to selectively induce apoptosis (programmed cell death) in many types of human cancer cells, with an insignificant effect on healthy non-cancerous cells. Major findings presented in this work are: the selectivity and efficacy of pancratistatin and synthetic derivatives on patient-obtained and commercially available leukemia; the potent effect of pancratistatin on human colon and prostate cancer cells in vitro and in vivo; and the unique mechanism of action of pancratistatin. In summary, pancratistatin is a natural anti-cancer compound that selectively targets cancer cell mitochondria to induce apoptosis and significantly reduces growth of human tumor xenografts.