Anti-proliferative effects of a new docosapentaenoic acid monoacylglyceride in colorectal carcinoma cells.
N-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to inhibit the induction and progression of many tumor types. However, the anticancer effect of n-3 PUFA monoglyceride on colorectal cancer has yet to be assessed. The aim of the present study was to determine the anti-tumorigenic effects of docosahexaenoic acid monoglyceride (MAG-DHA), eicosapentaenoic acid monoglyceride (MAG-EPA) and docosapentaenoic acid (22:5n-3) monoglyceride (MAG-DPA) in colorectal carcinoma cells. Our results demonstrate that MAG-DHA, MAG-EPA and MAG-DPA all decreased cell proliferation and induced apoptosis in HCT116 cells, with MAG-DPA having the higher anti-proliferative and pro-apoptotic effects in vitro. In a HCT116 xenograft mouse model, oral administration of MAG-DPA significantly inhibited tumor growth. Furthermore, MAG-DPA treatments decreased NFκB activation leading to a reduction in Bcl-2, CyclinD1, c-myc, COX-2, MMP9 and VEGF expression levels in tumor tissue sections. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in colorectal cancer cells.
SCF Pharma, Ste-Luce, QC, Canada G0K 1P0; Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4. Electronic address: cmorin@scfpharma.com.
Caroline
C
Morin
Éric
É
Rousseau
Samuel
S
Fortin
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004357:Drug Synergism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D050356:Lipid Metabolism / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D050178:Monoglycerides / Q000378:metabolism / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C000596377:1-O-docosapentaenoylglycerol; C588285:1-eicosapentaenoylglycerol; D000970:Antineoplastic Agents; D005227:Fatty Acids; D050178:Monoglycerides; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C575982:docosahexaenoic acid monoacylglyceride; C505407:CASP3 protein, human; D053148:Caspase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Apoptosis; Colorectal carcinoma; DPA; NFκB