Fate of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OMe) in malignant-cells, normal-cells, and isolated and perfused-rat-liver
Magistrelli, A; Villa, P; Benfenati, E; Modest, EJ; Salmona, M; Tacconi, MT
HERO ID
4936410
Reference Type
Journal Article
Year
1995
Language
English
PMID
| HERO ID | 4936410 |
|---|---|
| In Press | No |
| Year | 1995 |
| Title | Fate of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OMe) in malignant-cells, normal-cells, and isolated and perfused-rat-liver |
| Authors | Magistrelli, A; Villa, P; Benfenati, E; Modest, EJ; Salmona, M; Tacconi, MT |
| Journal | Drug Metabolism and Disposition |
| Volume | 23 |
| Issue | 1 |
| Page Numbers | 113-118 |
| Abstract | Ether lipids show high specific cytotoxicity in vitro on a wide variety of experimental tumors, but only moderate activity in vivo. One reason for this lack of activity in the whole animal might be a high degree of metabolic degradation. We therefore studied the biotransformation of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine ([H]ET18-OMe) labeled in position 9-10 of the 1-alkyl chain, in rat plasma and erythrocytes, HL60 and K562 leukemic cells. HT29 adenocarcinoma cells, and cultured hepatocytes at 37 degrees C, and in a system of isolated and perfused rat liver. ET18-OMe and its metabolites were identified and quantified after lipid extraction and TLC separation. In tumor cells, 98% of ET18-OMe remained almost unmodified in vitro after 24-hr incubation. Plasma and erythrocytes from rats metabolized only 4-5% of the original compound in 3 hr. In cultured hepatocytes, 35% and 58.3%, respectively, of ET18-OMe was present after 6 and 24 hr as the metabolites 1-O-alkyl-2-O-methylglycerol (AMG), 1-O-alkyl-2-O-methylphosphatidic acid (AMPA), and stearyl alcohol (SA) (products of direct hydrolysis by phospholipases C and D and alkylhydrolase); phospholipids (phosphatidylcholine and phosphatidylethanolamine); and neutral lipids (products of secondary metabolism). In perfused rat liver, similar to 15% of the total radioactivity incorporated after 3 hr was distributed in metabolites as follows: 5.9% of AMPA, 5.0% of AMG, and 3.1% of SA. We conclude that the metabolism of ET18-OMe in normal tissues occurring through the same enzymes that metabolize natural lipids may partly explain the lack of effect in vivo. |
| Pmid | 7720513 |
| Wosid | WOS:A1995QB45200016 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |