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 an d the differentiation of a neuroblastoma cell line (N18TG2). Mevalonat e and high density lipoproteins partially restore growth. Cholesterol synthesis in the presence of mevinolin remains active, because in thes e cells the key enzyme HMG-CoA reductase is not completely inhibited b y this drug. The fact that cell growth is reduced, while cholesterogen esis remains active, suggests that mevinolin acts by interfering with the synthesis of some unknown compound, other than cholesterol, which is necessary for proliferation.