Basic nutritional investigation -3 Polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells

Objective: This study evaluated whether -3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of -3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of -6 PUFAs. Methods: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with -3/-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multiva- riable linear regression analyses were used for comparison. Results: Preincubation with 30 to 100 mol/L of -3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P 0.05). Evaluation of the underlying mechanisms indicated that -3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 mol/L vitamin E abolished the effect of 50 mol/L of -3 PUFAs (P 0.05), whereas -6 PUFAs could partly mimic -3 PUFA effects. Conclusion: These observations suggest that -3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy. © 2006 Elsevier Inc. All rights reserved.

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