Differences in myristic acid synthesis and in metabolic rate for P388 cells resistant to doxorubicin.
Lipids extracted from doxorubicin-resistant murine leukemia cells (P388/ADR) contained greater relative amounts of myristic and palmitoleic acids than lipids from sensitive cells (P388). This was seen in both the phospholipid and neutral lipid fractions under two nutritional conditions. Correspondingly in P388/ADR cells, myristic acid comprised a greater proportion of the products of the fatty acid synthetase system, and acyl-CoA 9-desaturase activity was transiently greater than in P388. Similar alterations in myristic acid synthesis were exhibited by DC3F/AD X, N417/VP-16, and P388/AZQ30U cells but not by CHRC5 or HL60/AR cells. This alterations was independent of alterations in the P180 glycoprotein and might be linked via the myristoylation of proteins to a different mechanism of drug resistance. Doxorubicin-resistant P388/ADR cells also exhibited a much higher rate of oxidative energy production.
Wilder
P J
PJ
University of Maryland Cancer Center, Baltimore 21201.
Overman
D K
DK
Tenenholz
T C
TC
Gutierrez
P L
PL
D000085:Acetates / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007941:Leukemia P388 / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000032:analysis / Q000378:metabolism*; D010101:Oxygen Consumption; D010743:Phospholipids / Q000032:analysis; D014407:Tumor Cells, Cultured
D000085:Acetates; D005227:Fatty Acids; D008055:Lipids; D009227:Myristic Acids; D010743:Phospholipids; D019814:Myristic Acid; D004317:Doxorubicin; D044943:Fatty Acid Desaturases; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase