Growth inhibition of neuroblastoma cells by lovastatin and L-ascorbic acidis based on different mechanisms

Hydroxymethyl-glutaryl-CoA-reductase (HMG-CoA-reductase), the key enzyme fo r cholesterol synthesis and essential for the synthesis of the precursor fo r p21ras farnesylation, was inhibited in neuroblastoma cells by lovastatin or L-ascorbic acid. Both compounds inhibited clonogenic colony formation of neuroblastoma cells in soft agar. However, while the addition of mevalonat e, the product of HMG-CoA-reductase, circumvented the inhibition by lovasta tin it had no reversing effect on the inhibition by L-ascorbic acid. The ro le of reactive oxygen compounds generated by the degradation of catecholami nes, and the pro-oxidative effects of L-ascorbic acid are discussed as mech anisms of action of L-ascorbic acid. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.