R. Girgert et al., Growth inhibition of neuroblastoma cells by lovastatin and L-ascorbic acidis based on different mechanisms, CANCER LETT, 137(2), 1999, pp. 167-172
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.
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