Sanguinarine: A Novel Agent Against Prostate Cancer

摘要

The traditional therapeutic and surgical approaches have not been successful in the management of prostate cancer (CaP). Natural plant-based products have shown promise as anticancer agents. Sanguinarine, a benzophenanthridine alkaloid derived from the root of Sanguinaria Canadensis, has been shown to possess anti-microbial, antioxidant and anti-inflammatory properties. Our earlier studies suggested that sanguinarine may be developed as an agent for the management of prostate cancer. Based on this rationale, funded by the DOD (Award - W81XWH-04-1-0220), we initiated a study to investigate the hypothesis that sanguinarine will impart antiproliferative effects against prostate cancer via a modulation in NF-kB-pathway-mediated apoptosis. In the last three years, we have made reasonable progress towards our goals. However, the progress during this reporting period was hampered due to several unforeseen circumstances. Because of this reason, a one-year extension of the grant was obtained in January 2007. So far, the key accomplishments of our project are as follows. We have shown that sanguinarine possesses chemopreventive/anti-proliferative effects against CaP in an athymic nude mice xenograft model. Further, our data also suggested that sanguinarine-caused effects are mediated via modulations in NF-kB pathway and cki-cyclin-cdk machinery. At present, the studies are ongoing to assess the chemopreventive/therapeutic effects of sanguinarine on CaP development in transgenic TRAMP model.