Background: Radiotherapy is one of the primary therapies for
localized prostatic carcinoma. Therefore, there is an emerging need to sensitize
prostatic cancer cells to chemotherapy/radiotherapy. Modified citrus pectin
(MCP) is an effective inhibitor of galectin-3 (Gal-3), which is correlated with
tumor progression, proliferation, angiogenesis, and apoptosis.
Purpose: This study was directed to evaluate the efficacy of
combining ionizing radiation (IR) with MCP on PCa cells. Study
Design: Effects of treatments on PCa cells survival were evaluated
using XTT assay, flow cytometry, and clonogenic survival assay. Expression of
selected proteins was estimated using western blotting. Cell motility,
migration, and invasion were determined. Contribution of reactive oxygen species
production to treatment effects on cell viability was tested.
Results: Radiotherapy combined with MCP reduced viability and
enhanced radiosensitivity associated with a decrease in Gal-3, cleavage of the
precursor of caspase-3, increased expression of the pro-apoptotic protein Bax,
and downregulation of DNA repair pathways, poly-ADP-ribose polymerase, and
proliferating cell nuclear antigen. MCP significantly reduced the invasive and
migratory potential of PCa cells. Combining sodium pyruvate with MCP and IR
mitigated the effect on cell viability. Conclusion: Our findings
demonstrated that MCP sensitized PCa cells to IR by downregulating
anti-apoptotic Gal-3, modulating DNA repair pathways, and increasing ROS
production. For the first time the correlation between MCP, radiotherapy, and
Gal-3 for prostatic cancer treatment was found. In addition, MCP reduced the
metastatic properties of PCa cells. These findings provide MCP as a
radiosensitizing agent to enhance IR cytotoxicity, overcome radioresistance, and
reduce clinical IR dose.