Growth inhibition of neuroblastoma cells by lovastatin and l-ascorbic acid is based on different mechanisms

Hydroxymethyl-glutaryl-CoA-reductase (HMG-CoA-reductase), the key enzyme for cholesterol synthesis and essential for the synthesis of the precursor for 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 mevalonate, the product of HMG-CoA-reductase, circumvented the inhibition by lovastatin it had no reversing effect on the inhibition by l-ascorbic acid. The role of reactive oxygen compounds generated by the degradation of catecholamines, and the pro-oxidative effects of l-ascorbic acid are discussed as mechanisms of action of l-ascorbic acid.