Characterization of the response of growth and differentiation to lipoproteins and agents affecting cholesterol metabolism in murine neuroblastoma cells.
Treatment with mevinolin, a competitive inhibitor of HMGCoAR, the key enzyme of isoprenoid metabolism, causes the arrest of proliferation and the differentiation of a neuroblastoma cell line (N18TG2). Mevalonate and high density lipoproteins partially restore growth. Cholesterol synthesis in the presence of mevinolin remains active, because in these cells the key enzyme HMG-CoA reductase is not completely inhibited by this drug. The fact that cell growth is reduced, while cholesterogenesis remains active, suggests that mevinolin acts by interfering with the synthesis of some unknown compound, other than cholesterol, which is necessary for proliferation.
Castellano
F
F
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Roma, Italy.
Bruscalupi
G
G
Columba
S
S
Di Croce
L
L
Trentalance
A
A
Augusti-Tocco
G
G
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D002784:Cholesterol; D008148:Lovastatin; D008798:Mevalonic Acid