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.
Girgert
R
R
Department of Pediatric Surgery, Klinikum Schmarrenberg, University of Tübingen, Germany.
Vogt
Y
Y
Becke
D
D
Bruchelt
G
G
Schweizer
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C015367:mevalonolactone; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D001205:Ascorbic Acid; D008798:Mevalonic Acid