Incorporation of polyunsaturated fatty acids into CT-26, a transplantable murine colonic adenocarcinoma.
Previous studies in our laboratory have shown that marine oils, with high levels of eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acids (DHA, 22:6n-3), inhibit the growth of CT-26, a murine colon carcinoma cell line, when implanted into the colons of male BALB/c mice. An in vitro model was developed to study the incorporation of polyunsaturated fatty acids (PUFA) into CT-26 cells in culture. PUFA-induced changes in the phospholipid fatty acid composition and the affinity with which different fatty acids enter the various phospholipid species and subspecies were examined. We found that supplementation of cultured CT-26 cells with either 50 microM linoleic acid (LIN, 18:2n-6), arachidonic acid (AA, 20:4n-6), EPA, or DHA significantly alters the fatty acid composition of CT-26 cells. Incorporation of these fatty acids resulted in decreased levels of monounsaturated fatty acids, while EPA and DHA also resulted in lower levels of AA. While significant elongation of both AA and EPA occurred, LIN remained relatively unmodified. Incorporation of radiolabeled fatty acids into different phospholipid species varied significantly. LIN was incorporated predominantly into phosphatidylcholine and had a much lower affinity for the ethanolamine phospholipids. DHA had a higher affinity for plasmenylethanolamine (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) than the other fatty acids, while EPA had the highest affinity for phosphatidylethanol-amine (1,2-diacyl-sn-glycero-3-phosphoethanolamine). These results demonstrate that, in vitro, significant differences are seen between the various PUFA in CT-26 cells with respect to metabolism and distribution, and these may help to explain differences observed with respect to their effects on tumor growth and metastasis in the transplantable model.
Gaposchkin
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The Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
Zoeller
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Broitman
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D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000493:pharmacokinetics; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid