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

被引:20
作者
Girgert, R
Vogt, Y
Becke, D
Bruchelt, G
Schweizer, P
机构
[1] Univ Tubingen, Klinikum Schnarrenberg, Dept Pediat Surg, Oncol Lab, D-72076 Tubingen, Germany
[2] Univ Tubingen, Childrens Hosp, Dept Hematol, D-72076 Tubingen, Germany
关键词
neuroblastoma; HMG-CoA-reductase; lovastatin; L-ascorbic acid; reactive oxygen;
D O I
10.1016/S0304-3835(98)00355-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:167 / 172
页数:6
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