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Anti-tumor effect of novel cationic biomaterials in prostate cancer
Gunjan Gakhar1, Huixian Liu2, Roquian Shen1
1Department of Medicine, Weill Cornell Medical College, New York City, NY, U.S.A.
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.
Insights
Newly synthesized cationic polymers selectively target prostate cancer cells, reducing viability and inducing apoptosis. This approach of targeting anionic-charged tumor cells shows promise for novel prostate cancer therapies.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Drug Delivery
Background:
- Tumor cells with high anionic-charged sialic acid can be targeted by cationic polymers.
- Cationic polymers may inhibit tumor growth by interacting with these cells.
Purpose of the Study:
- To synthesize novel cationic polymers.
- To evaluate their effects on prostate cancer cells (PC3) and normal prostate epithelial cells (RWPE-1).
Main Methods:
- Cell viability assays
- DNA fragmentation assays
- Apoptosis assays
- Confocal microscopy
Main Results:
- Dextran-based polymer (Dex-PA-3X) and vinyl-based PolyAETA significantly reduced PC3 cell viability and increased cell death compared to RWPE-1 cells.
- Polymers induced apoptosis at lower concentrations and both apoptosis and necrosis at higher concentrations.
- Dex-PA-3X localized in PC3 cytoplasm, while PolyAETA localized in both cell types, with lower intensity in RWPE-1.
Conclusions:
- The synthesized cationic polymers Dex-PA-3X and PolyAETA selectively bind to prostate cancer cells.
- These polymers reduce cancer cell viability and induce apoptosis.
- Targeting negatively-charged tumor cells represents a novel strategy for prostate cancer treatment.
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