Induced oxidative stress and cell death in the A549 lung adenocarcinoma cell line by ionizing radiation is enhanced by supplementation with docosahexaenoic acid.
Both ionizing radiation and docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid (PUFA), have been shown to inhibit tumor cell growth at least in part by increasing oxidative stress. In this study, the effects of ionizing radiation, DHA, or a combination of the two on cell proliferation, anchorage-independent growth, apoptosis, and lipid peroxidation in A549 lung adenocarcinoma cells were examined. In this study, significant decreases in cell proliferation and colony formation were noted for ionizing radiation or DHA treatments, whereas a combination of the two showed significant reductions over either treatment alone. Conversely, lipid peroxidation and apoptotic cell death showed significant increases with ionizing radiation and DHA treatments, whereas cells receiving both treatments demonstrated further significant increases. Moreover, addition of vitamin E, an antioxidant, was able to completely reverse lipid peroxidation and cell death due to ionizing radiation and partially reverse these changes in DHA treatments. Finally, the preferential incorporation of DHA into lung and xenograft compared to liver tissue is demonstrated in an in vivo model. These findings confirm the potential of DHA supplementation to enhance the treatment of lung cancer using ionizing radiation by increasing oxidative stress and enhancing tumor cell death.
University of Nevada, Reno, Nevada 89557, USA. kkikawa@unr.edu
Keith D
KD
Kikawa
J S
JS
Herrick
R E
RE
Tateo
M
M
Mouradian
J S
JS
Tay
R S
RS
Pardini
D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004032:Diet; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000528:radiation effects*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000627:therapeutic use*; D011897:Random Allocation; D014810:Vitamin E / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D011838:Radiation-Sensitizing Agents; D014810:Vitamin E; D004281:Docosahexaenoic Acids