Anti-Cancer Effects of a New Docosahexaenoic Acid Monoacylglyceride in Lung Adenocarcinoma

Abstract

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.

Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

“…Western blots using specific antibodies against EGFR, ERK1/2, β-actin and phosphorylated forms of EGFR and ERK1/2 (all from New England BioLabs, Pickering, ON, Canada) were performed on cell lysate fractions as previously described (8).…”

“…shown that omega-3 PUFA supplementation prevent or reduce the growth of tumor cells (2,3,(5)(6)(7)(8). Moreover, clinical studies have demonstrated significant protective effects of omega-3 fatty acids against lung cancer and high omega-3 intake was associated with a lower risk of lung cancer (3,4,21).…”

“…Some studies link the tumor-suppressive activity of omega-3 PUFAs with the mitogen-activated protein kinase pathway and either the activation or inactivation of its components with the induction of apoptosis (5) and growth arrest (6). Our previous studies have demonstrated that well-absorbed omega-3 PUFAs, docosapentaenoic acid monoglyceride (MAG-DPA) and MAG-DHA are able to exert anti-proliferative and pro-apoptotic effects on colorectal and lung cancer cells through the downregulation of NFĸB and up-regulation of PTEN (7,8).…”

Docosapentaenoic acid monoacylglyceride reduces inflammation and vascular remodeling in experimental pulmonary hypertension

“…The aim of the present study was thus to evaluate the effects of MAG-DPA on pulmonary inflammation and remodeling occurring in PH. Fatty acids in monoacylglyceride form are generally recognized as safe and are widely used as emulsifying agents in the food industry (40). Moreover, PUFA monoacylglycerides have been demonstrated to increase the oral bioavailability of PUFA compared with commercially available marine oil (15,16,40).…”

“…Fatty acids in monoacylglyceride form are generally recognized as safe and are widely used as emulsifying agents in the food industry (40). Moreover, PUFA monoacylglycerides have been demonstrated to increase the oral bioavailability of PUFA compared with commercially available marine oil (15,16,40). For the purposes of this study, an in vivo model of PH induced by monocrotaline (MCT) was used as experimental setting.…”