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. 2018 Dec;17(4):1225-1234.
doi: 10.1177/1534735418790382. Epub 2018 Jul 25.

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

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Free PMC article

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

Sefora Conti et al. Integr Cancer Ther. .
Free PMC article

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.

Keywords: galectin-3; ionizing radiation; modified citrus pectin; prostate cancer; radiosensitivity.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The author Isaac Eliaz acknowledges that he is the owner of a medical clinic and dietary supplement company. The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Effect of MCP (B) and IR (A) alone on PCa cells viability. Cell viability was evaluated by XTT assay. The graphs represent mean ± SE survival values of irradiated/treated cells from 3 experiments each performed in triplicate (*P < .05; **P < .01; ***P < .001).
Figure 2.
Figure 2.
Combined effect of MCP and IR on cell viability. (A, B, and C) Survival of cells evaluated by XTT assay. (D, E, and F) Normalized isobolograms indicating mode of treatments interaction.
Figure 3.
Figure 3.
Effect of MCP and IR on DU-145 cell survival evaluated by clonogenic assay. Cell survival after MCP (A) and IR (B) treatments alone and after combined treatment (C).
Figure 4.
Figure 4.
Induction of apoptosis in DU-145 cells treated by MCP. (A) PI staining and (B) double Annexin-V-FITC/7-AAD staining. Double-negative cells are intact cells, Annexin-V-FITC positive cells indicated early apoptosis, double-positive cells indicated late apoptosis, and 7-AAD positive cells indicated necrotic cells.
Figure 5.
Figure 5.
Effect of MCP on migration (A) and invasion (B) of DU-145 cells in vitro. Migration and invasion were evaluated using Transwell assay with or without Matrigel coating of membrane. Representative images of migrated (A) or invaded (B) MCP treated cells are shown.
Figure 6.
Figure 6.
Effect of pyruvate on viability of DU-145 cells treated by MCP (A) or IR (B). Cell viability was evaluated by XTT assay. Viability of cells treated with 25 µM H2O2 was used as a positive control. The data are mean ± SE values from 3 individual experiments.
Figure 7.
Figure 7.
Effect of IR and MCP on expression of selected proteins in DU-145 cells. Cell lysates were subjected to western blot analysis: (A) with mouse antihuman PARP and (B) with β-mouse antihuman PCNA; (C) with antihuman caspase-3 and (D) antihuman Bax; (E) nuclear extract with antihuman Gal-3 and (D) cytoplasmic extract with antihuman Gal-3.

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