Abstract 5637: Plumbagin, a plant derived napthoquinone, inhibits the metastatic growth of human prostate cancer PC-3M luciferase cells in an orthotropic xenograft mouse model

Prostate cancer (PCa) is the second most common malignancy in men and the second leading cause of cancer-related deaths in the Western World. Androgen ablation therapy remains the gold standard for the treatment of PCa. Despite the initial success of androgen ablation therapy, resistance to anti-androgen therapy manifests by progression to hormone refractory PCa, which accounts for majority of PCa patient deaths. Plumbagin (PL), a novel plant derived napthoquinone isolated from the roots of medicinal plant Plumbago zeylanica L has been shown for its anti-cancer activity against various types of cancer. We have previously shown that PL induces apoptosis and inhibits the growth of human PCa cells in vitro as well as in vivo model systems. PL treatment also inhibited the spontaneous development of prostate tumor in the TRAMP mouse model. Here, we determined the anti-metastatic potential of PL in an orthotopic xenograft mouse model. Highly aggressive and metastatic PCa PC3M luciferase cells (2X10 6 ) were injected into the prostate of athymic nude mice. Three days post-injection, mice were randomly divided into two groups. One group of mice was administered with PL (2 mg/kg body wt. i.p five days in a week) in 0.1 ml of PBS containg 10% DMSO for 7 weeks. Vehicle group mice were administered with 0.1 ml of PBS containg 10 % DMSO. Prostate tumor development and distant metastasis into liver, lungs, and lymph nodes were examined weekly by bioluminescence imaging of live mice and compared with vehicle treated mice. We observed that PL treatment significantly inhibited the growth of PC3M cells xenograft tumors and metastasis as determined by significantly reduced photon intensity in PL-treated mice compared to control group mice. We also performed bioluminescence imaging of excised prostate, liver, lungs and lymph nodes for distant metastasis quantification. Results demonstrated that PL significantly inhibited prostate tumor growth and distant metastasis in lungs compared with vehicle treated mice. These results were further confirmed by histopathology. All the control and PL-treated groups’ mice demonstrated orthotopic tumor formation in the mouse prostates. Control mice showed large metastasis foci in the lungs, liver and lymph nodes. None of the mice from PL-treated group showed metastasis in the liver, but these mice showed significantly less and smaller size of metastatic foci in the lungs compared to control mice. All the enlarged regional lymph nodes were positive for metastasis in both PL-treated and control mice. Our data suggest that PL has an anti-metastatic potential against PCa. PL could be used as a novelchemopreventive natural agent for the treatment of PCa. (Support: NIH grant, CA138761). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5637. doi:1538-7445.AM2012-5637