Sanguinarine: A Novel Agent Against Prostate Cancer; Final rept. 16 Jan 2004-31 Dec 2007

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. During the funding period, 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 also obtained in January 2007. So far, the key accomplishments of our project are as follows. We have demonstrated that sanguinarine possesses anti- proliferative effects against CaP in an athymic nude mice xenograft model. Further, our data suggested that sanguinarine-caused effects may be mediated via modulations in NF-B pathway and cyclin kinase inhibitor-cyclin-cyclin dependent kinase machinery. Our study with transgenic TRAMP model has suggested that sanguinarine may be developed as an agent for the management of CaP.