Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells.
OBJECTIVE
This study evaluated whether omega-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 omega-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 omega-6 PUFAs.


METHODS
LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-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 multivariable linear regression analyses were used for comparison.


RESULTS
Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-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 micromol/L vitamin E abolished the effect of 50 micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects.


CONCLUSIONS
These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.
Benais-Pont
Gaëlle
G
Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland.
Dupertuis
Yves M
YM
Kossovsky
Michel P
MP
Nouet
Philippe
P
Allal
Abdelkarim S
AS
Buchegger
Franz
F
Pichard
Claude
C
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D011839:Radiation, Ionizing; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D014810:Vitamin E