Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advances in research, diagnosis
and treatment, lung cancer remains a highly lethal disease, often diagnosed at advanced stages and with a very poor prognosis.
Therefore, new strategies for the prevention and treatment of lung cancer are urgently needed. The aim of the present
study was to determine the anti-tumorigenic effects of docosahexaenoic acid monoacylglyceride (MAG-DHA), a
newly patented DHA derivative in lung adenocarcinoma. Our results demonstrate that MAG-DHA treatments decreased
cell proliferation and induced apoptosis in A549 human lung carcinoma cells whereas MAG-DHA treatment did not induce
apoptosis of normal bronchial epithelial BEAS-2B cells. MAG-DHA decreased NFκB activation leading to a reduction
in COX-2 expression level in both A549 cells and lung adenocarcinoma tissues. Furthermore, MAG-DHA treatment
increased PTEN expression and activation concomitant with a decrease in AKT phosphorylation levels and enhanced
apoptosis. Oral administration of MAG-DHA significantly reduced tumor growth in a mouse A549 xenograft model.
Lastly, MAG-DHA markedly decreased COX-2 and enhanced PTEN protein expression in tumor tissue sections. Altogether,
these data provide new evidence regarding the mode of action of MAG-DHA and strongly suggest that this compound
could be of clinical interest in cancer treatment.
Keywords: Apoptosis, COX-2, DHA, lung adenocarcinoma, PTEN.
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