Severe modifications of ether- ester- or diester-linked glycerolipid and non glycerolipid synthesis in human neuroblastoma LAN-1 cells cultured with octadecylmethylglycerophosphocholine.
The growth rate of the human neuroblastoma LAN-1 cells was decreased half after 48 h of incubation with dialkylglycerophosphocholine 1-O-octadecyl 2-O-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3), at 4 microM. Four radiolabelled precursors, [3H]hexadecanol, [3H]hexadecanoic, [3H]arachidonic acids, or N-acetyl[14C] neuraminic acid were added in the culture medium to follow their cell incorporation among various glycerolipids, gangliosides and eicosanoids. Several modifications of the glycerophospholipid synthesis induced by ET-18-O-CH3 were observed. The inhibition of 1-O-[3H]hexadecanoyl 2-O-acyl glycerophosphocholine synthesis provoked the accumulation of diacylglycerophosphoethanolamine. The inhibition of 1-O-[3H]hexadecyl 2-O-acyl glycerophosphocholine and ethanolamine synthesis enhanced the synthesis of non phosphorous glycerolipids with 1-O-[3H]hexadecyl-sn-glycerol backbone. The eicosanoid synthesis was not disturbed. Alterations of ether- ester- and diester-linked glycerophospholipid and non phosphorous glycerolipid synthesis could modify the lipid membrane distribution and affect the enzymatic pathway of the ceramide synthesis. An excess of [3H]hexadecanoyl-amide molecular species of ceramides in mono- and disialo-gangliosides was observed. By contrast the N-acetyl [14C]neuraminosyl-linkage in these two groups of gangliosides never reached the hypersialylation process described during sialoglyco-peptide synthesis in murine carcinoma kidney cell lines. Both metabolic disturbances of the glycerolipid and ganglioside synthesis reported for the neuroblastoma LAN-1 cell line sensitive to ET-18-O-CH3 extend and confirm the previous studies with other more resistant cell lines from the murine Meth A sarcoma and the rat colon carcinoma.
Boucrot
P
P
Laboratoire des interactions des molécules alimentaires, INRA, Nantes, France.
Aubry
J
J
Mezazigh
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002518:Ceramides / Q000378:metabolism; D004952:Esters; D004987:Ethers; D005732:Gangliosides / Q000378:metabolism; D005994:Glycerophosphates / Q000096:biosynthesis*; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002518:Ceramides; D004952:Esters; D004987:Ethers; D005732:Gangliosides; D005994:Glycerophosphates; D010742:Phospholipid Ethers; C026659:edelfosine; D016718:Arachidonic Acid; D019308:Palmitic Acid; D019158:N-Acetylneuraminic Acid