洛伐他汀和L-抗坏血酸对神经母细胞瘤细胞的生长抑制作用基于不同的机制。

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

作者信息

Girgert R, Vogt Y, Becke D, Bruchelt G, Schweizer P

机构信息

Department of Pediatric Surgery, Klinikum Schmarrenberg, University of Tübingen, Germany.

出版信息

Cancer Lett. 1999 Apr 1;137(2):167-72. doi: 10.1016/s0304-3835(98)00355-3.

DOI:10.1016/s0304-3835(98)00355-3

PMID:10374838

Abstract

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.

摘要

羟甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）是胆固醇合成的关键酶，也是p21ras法尼基化前体合成所必需的酶，在神经母细胞瘤细胞中被洛伐他汀或L-抗坏血酸抑制。这两种化合物都抑制了神经母细胞瘤细胞在软琼脂中的克隆集落形成。然而，虽然添加HMG-CoA还原酶的产物甲羟戊酸可规避洛伐他汀的抑制作用，但对L-抗坏血酸的抑制作用却没有逆转效果。文中讨论了儿茶酚胺降解产生的活性氧化合物的作用以及L-抗坏血酸的促氧化作用，作为L-抗坏血酸的作用机制。