Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer

Abstract

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.

Lectin affinity chromatography and quantitative proteomic analysis reveal that galectin-3 is associated with metastasis in nasopharyngeal carcinoma

“…The released Galectin-3 can bind to components of extracellular matrix and its membrane counterparts of other cells, which have in a wide range of biological events including cellular homeostasis, immune function, angiogenesis, tumor invasion and metastasis 25 . Galectin-3 has been reported as a diagnostic or prognostic marker linked to metastasis in many types of cancer such as thyroid 26,27 , breast cancer 28 , melanoma 29 , lung cancer 30 , sarcoma 31 , gastric cancer 32 , prostate cancer 33 and oral tongue cancer 34 . Here, we showed that Galectin-3 was greatly expressed in highly metastatic NPC cells compared to lowly metastatic cells.…”

Galectins in Cancer and the Microenvironment: Functional Roles, Therapeutic Developments, and Perspectives

“…In agreement with other reports, the authors also showed that GCS-100, an antagonist of Gal-3, induced cancer cell death [ 190 , 191 , 192 ], boosted tumor-infiltrating T lymphocyte secretion of IFN-gamma [ 143 ], and increased prostate cancer sensitivity to cisplatin [ 193 ]. Similarly, an effect was observed in response to modified citrus pectin (MCP) on cancer [ 67 , 95 , 194 , 195 ]; however, MCP can also be used for other Gal-related disease treatments, such as decreasing Gal-3 levels in type 2 diabetes [ 196 ], decreasing doxorubicin-induced cardiovascular diseases [ 197 ], ameliorating cardiac dysfunction [ 198 ], and improving ischemic heart failure [ 199 ]. In addition, the calixarene derivative compound “OTX-008” was designed as a Gal-1 inhibitor [ 200 ].…”

Pleiotropic Effects of Modified Citrus Pectin

“…Moreover, MCP reduced prostate cancer cell viability and synergistically enhanced cell sensitivity to ionizing radiation [10]. Inhibition with the MCP of extracellular Gal-3 decreased colon cancer cell migration [9].…”