N-Butyldeoxynojirimycin inhibits murine melanoma cell ganglioside metabolism and delays tumor onset

被引：34

作者：

Guerrera, M ^{[1
]}

Ladisch, S ^{[1
]}

机构：

[1] Childrens Natl Med Ctr, Childrens Res Inst, Glycobiol Program, Ctr Canc & Transplantat Biol, Washington, DC 20010 USA

来源：

CANCER LETTERS | 2003年 / 201卷 / 01期

关键词：

tumor gangliosides; melanoma; glucosylceramide synthase; N-butyldeoxynojirimycin; tumor model;

D O I：

10.1016/S0304-3835(03)00459-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aberrant ganglioside metabolism is linked to tumor progression. Since ganglioside depletion reduced tumorigenicity of MEB4 murine melanoma cells, we studied N-butyldeoxynojirimycin (NB-DNJ), an imino sugar administered orally to inhibit glucosylceramide (GlcCer) synthase in patients with glycosphingolipid storage diseases, for effects on MEB4 melanoma tumor cell ganglioside metabolism, cell biology, and tumorigenesis. Here we show that 50 muM NB-DNJ reduced MEB4 cell GlcCer synthase activity (by 70%), ganglioside synthesis (by 61%), and shedding (by 37%) while ceramide concentrations and cell viability were unaffected. Partial ganglioside depletion caused a delay in tumor onset but not in tumor incidence, possibly because of rapid (48 h) ganglioside recovery. The delay in tumor development by NB-DNJ treatment of MEB4 cells provides further support for the concept of tumor cell ganglioside metabolism as a therapeutic target in cancer. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

引用

页码：31 / 40

页数：10

共 59 条

[1] Glycosphingolipid depletion in Fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase [J].