Anti-tumor effect of novel cationic biomaterials in prostate cancer

Anticancer Res. 2014 Aug;34(8):3981-9.

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.

Keywords: Amino acid-based poly (ester-amide)s; apoptosis; arginine; cationic polymers; chitosan; cytotoxicity; dextran; lysine; necrosis; polysaccharides; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biocompatible Materials / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Male
  • Polymers / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Polymers