Gunjan Gakhar1, Huixian Liu2, Roquian Shen1, Douglas Scherr2, Dequn Wu3, David Nanus1, Chih-Chang Chu4. 1. Department of Medicine, Weill Cornell Medical College, New York City, NY, U.S.A. 2. Department of Urology, Weill Cornell Medical College, New York City, NY, U.S.A. 3. Biomedical Engineering Program and Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY, U.S.A. 4. Biomedical Engineering Program and Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY, U.S.A. cc62@cornell.edu.
Abstract
BACKGROUND: Tumor cells expressing excessive anionic-charged sialic acid can be potentially targeted by cationic polymers which may inhibit tumor growth. In the present study, three new families of cationic polymers were synthesized to assess their effects on prostate cancer cells. MATERIALS AND METHODS: Cationic polymers effects on PC3 prostate cancer cells and normal prostate epithelial cell (RWPE-1) were assessed using cell viability, DNA fragmentation, apoptosis assays and confocal microscopy. RESULTS: The dextran-based polymer (Dex-PA-3X) (40 μg/ml) and the vinyl-based PolyAETA (5 μg/ml) induced a significant reduction in cell viability in PC3 cells (85% and 50%, respectively; p<0.05) in comparison to RWPE-1 cells. Furthermore, Dex-PA-3X induced a 50%, and PolyAETA induced a 35% increase in cell death in PC3 cells compared to RWPE-1 cells measured by DNA fragmentation assay. Lower concentrations of both polymers induced apoptosis while higher concentrations induced both apoptosis and necrosis by immunostaining. Confocal microscopy indicated the localization of Dex-PA in the cytoplasm of PC3 but not RWPE-1 cells, while PolyAETA was seen in both PC3 and RWPE-1 cells, but at lower intensity in RWPE-1 cells. CONCLUSION: The newly-synthesized cationic polymers Dex-PA-3X and PolyAETA selectively bind to, reduce viability and induce cell apoptosis in prostate cancer cells, suggesting that targeting negatively-charged tumor cells could be a novel strategy to treat prostate cancer. Copyright
BACKGROUND:Tumor cells expressing excessive anionic-charged sialic acid can be potentially targeted by cationic polymers which may inhibit tumor growth. In the present study, three new families of cationic polymers were synthesized to assess their effects on prostate cancer cells. MATERIALS AND METHODS: Cationic polymers effects on PC3prostate cancer cells and normal prostate epithelial cell (RWPE-1) were assessed using cell viability, DNA fragmentation, apoptosis assays and confocal microscopy. RESULTS: The dextran-based polymer (Dex-PA-3X) (40 μg/ml) and the vinyl-based PolyAETA (5 μg/ml) induced a significant reduction in cell viability in PC3 cells (85% and 50%, respectively; p<0.05) in comparison to RWPE-1 cells. Furthermore, Dex-PA-3X induced a 50%, and PolyAETA induced a 35% increase in cell death in PC3 cells compared to RWPE-1 cells measured by DNA fragmentation assay. Lower concentrations of both polymers induced apoptosis while higher concentrations induced both apoptosis and necrosis by immunostaining. Confocal microscopy indicated the localization of Dex-PA in the cytoplasm of PC3 but not RWPE-1 cells, while PolyAETA was seen in both PC3 and RWPE-1 cells, but at lower intensity in RWPE-1 cells. CONCLUSION: The newly-synthesized cationic polymersDex-PA-3X and PolyAETA selectively bind to, reduce viability and induce cell apoptosis in prostate cancer cells, suggesting that targeting negatively-charged tumor cells could be a novel strategy to treat prostate cancer. Copyright