Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines

Abstract

Background & aims: This study aims at evaluating if docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) increases the efficacy of radiation therapy (RT) on two human colorectal cancer cell lines with different radio-sensitivity.

Methods: LS174T and HT-29 cells were treated with 20 or 50 μmol/L EPA or DHA followed by single X-ray RT of 0, 2 or 4 Gy, to evaluate cell survival, apoptosis, peroxide and malondialdehyde productions. Inflammation- and apoptosis-related proteins were analyzed by Western Blot. ANOVAs were used for statistical analysis.

Results: LS174T was more sensitive to RT than HT-29. DHA and to a lesser extent EPA increased cell death, apoptosis and peroxide production after RT in LS174T and to a lesser extent in HT-29 (p < 0.05). This was associated with increased expression of heat shock protein 70, decreased expression of NF-kB p65, COX-2 and Bcl-2 proteins.

Conclusions: The effect of RT combination with DHA and to a lesser extent EPA was synergistic in the radio-sensitive LS174T cells, but additive in the radio-resistant HT-29 cells. This enhanced cytotoxicity was provoked at least partly by lipid peroxidation, which consequently modulated inflammatory response and induced apoptosis.

Keywords: 2,4-dinitrophenylhydrazine; CRC; DHA; DNPH; Docosahexaenoic acid; EDTA; EPA; Eicosapentaenoic acid; Ethylenediaminetetraacetic acid; FACS; FITC; HPLC; Human colorectal adenocarcinoma; Lipid peroxidation; MDA; PBS; RT; Radiation therapy; SDS-PAGE; colorectal adenocarcinoma; docosahexaenoic acid; eicosapentaenoic acid; fluorescein isothiocyanate; fluorescence-activated cell sorting; high-performance liquid chromatography; malondialdehyde; phosphate-buffered saline; radiation therapy; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; ω-3 PUFAs; ω-3 polyunsaturated fatty acids.