Abstract 5555: Combined effect of modified citrus pectin and ionizing radiation on survival and metastatic activity of prostate cancer cells

Abstract

Abstract Radio-resistance is a major cause of decreasing the efficiency of radiotherapy for prostate cancer. Modified citrus pectin (MCP) has been previously shown to demonstrate anti-proliferative and anti-metastatic activity in prostate cancer cells. However, its combination with radiation has not been evaluated. The aim of the present study was to investigate whether MCP radiosensitized prostate cancer cell lines and to unravel its underlying mechanism(s). XTT cell proliferation and clonogenic assays were used to assess MCP effect alone and in combination with radiation on viability of prostate cancer cell lines (DU-145, PC-3 and Cl-1). Calcusyn software analysis was used to determine the mode of interaction between the treatments tested. Flow cytometry analysis with propidium iodide staining, annexin-V-FITC and 7-aminoactinomycin D (7-AAD) double staining were used to evaluate effect on cell cycle, apoptosis and necrosis. Standard Transwell Assay with and without Matrigel was used to assess effect of MCP on invasiveness of cells. The effect of MCP and radiation on reactive oxygen species (ROS) production, and expression of galectin-3, PARP, caspase-3, caspase-9, Bak, Bax, and Bcl-2 and NF-κB pathways in treated cells are currently being investigated, and will be included in the presentation. Treatment of DU-145, PC-3 and Cl-1 prostate cancer cells with MCP induced a dose dependent decrease in cell viability tested by XTT assay (IC50 values were 1.07, 1.48, 1.29 mg/ml respectively). These cells demonstrated similar radio-sensitivity. The effect of the combined treatment were either synergistic (Combined index∼0.7, DU-145 and Cl-1 cells) at high dose (2 mg/ml) of MCP or additive (Combined index 1.1-0.9, PC-3 cells). Flow cytometric analysis showed that neither MCP nor radiation either alone or combined resulted in significant changes in cell cycle distribution. Double staining of DU-145 cells with annexin-V-FITC and 7-AAD revealed effect of combined treatment on apoptosis and necrosis. Treatment of cells with 2 mg/ml MCP reduced 20% of migrating cells and 40% of invasive cells. The effects of MCP and radiation on ROS production, pro-apoptotic and NF-κB pathways in treated cells are currently being investigated. These results suggest that MCP is a radiosensitizer in prostate cancer cells. Its mechanism of action is being investigated, and will be included in this presentation. Citation Format: Isaac G. Eliaz, Sefora Conti, Akiva Vexler, Ben Koren, Nir Honig, Natan Shtraus, Yaron Meir, Shahar Lev-Ari, Ilan Ron. Combined effect of modified citrus pectin and ionizing radiation on survival and metastatic activity of prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5555. doi:10.1158/1538-7445.AM2015-5555