Hexadecanoic and neuraminic acid incorporations in two rat colon carcinoma cell lipids: selective influence of 1-O-octadecyl 2-O-methyl-3-phosphocholine on glycerolipid and ganglioside biosynthesis.
[3H] hexadecanoic and N-acetyl [14C] neuraminic acids were incorporated in glycerolipids or gangliosides of 2 rat colon carcinoma cell lines, having (PRO cells), or not (REG cells) invasive capacities when inoculated in syngeneic BD IX rats. The cells were cultured (48 h) in presence of 1-0-octadecyl-2-0-methyl-3-phosphocholine (ET 18-0-CH3) 20 or 40 microM, which, on transformed cells, inhibits the cell growth, modifies the glycerolipid biosynthesis, and activates the sialyltransferases. ET 18-0-CH3 20 microM activated, in PRO and in REG cells the incorporation of [3H] hexadecanoate in monosialogangliosides (1.45 fold compared to controls), but not in disialogangliosides and the distribution of this fatty acid between monosialo- (82%) and disialogangliosides (18%) was unchanged with controls. After [14C] neuraminic acid labelings, and for control experiments, the total radioactivities in gangliosides, in PRO cells, were twice higher than in REG cells, a difference which, probably, reflects the ganglioside content. ET 18-0-CH3 20 microM did not increase the incorporation of the [14C] neuraminic acid in PRO and in REG cells, and did not change its distribution between monosialo (70-80% for controls and experiments with ET 18-0-CH3) and disialogangliosides (20-30%). Similar results were obtained with ET 18-0-CH3 40 microM for the distribution of [14C] neuraminic acid in monosialo- and disialogangliosides. Whatever the precursor, the trisialogangliosides were never radiolabeled. Analysis of the [3H] glycerolipids (the main radiolabeled lipid classes in controls were: phosphatidylcholines, triglycerides, sphingomyelins and phosphatidyl-inositols) revealed that ET 18-0-CH3, compared to controls, did not activate the incorporation of [3H] hexadecanoate in total glycerolipids (PRO or REG cells). It activated (3 fold) its incorporation in triglyerides, inhibited it (0.5-0.6 fold) in phosphatidylcholines, sphingomyelins and phosphatidyl-inoditols and all these most noticeable differences were observed in PRO and in REG cells. These findings reflect the impossibility of ET 18-0-CH3 to activate the sialyltransferases during the ganglioside biosynthesis in colon carcinoma cells, while it modified ceramide, glycerophospholipid and neutral glycerolipid biosynthesis.
Mjabri
B
B
Laboratoire de Biochimie Médicale, INSERM Faculté de Médecine -Pharmacie, Nantes, France.
Boucrot
P
P
Aubry
J
J
D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism*; D005732:Gangliosides / Q000096:biosynthesis*; D008055:Lipids / Q000096:biosynthesis*; D009438:Neuraminic Acids / Q000378:metabolism*; D010169:Palmitic Acids / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D005732:Gangliosides; D008055:Lipids; D009438:Neuraminic Acids; D010169:Palmitic Acids; D010742:Phospholipid Ethers; C026659:edelfosine