文章基本信息

标题：A Synthetic Glycosphingolipid-Induced Antiproliferative Effect in Melanoma Cells Is Associated with Suppression of FAK, Akt, and Erk Activation
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作者：Yoshiko Sonoda ; Noriyasu Hada ; Tomonori Kaneda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：6
页码：1279-1283
DOI：10.1248/bpb.31.1279
出版社：The Pharmaceutical Society of Japan
摘要：Numerous studies have demonstrated the participation of glicolipids in signal transduction and the regulation of melanoma cell growth and apoptosis. Hoping to discover new anticancer drugs, we have synthesized ten glycolipids found in various invertebrates that do not have sialic acids. These compounds were tested for antiproliferative effects on a melanoma cell line, B16F10. A synthetic compound, Manβ(1–4)[Fucα(1–3)]Glcβ1-Cer, (glycosphingolipid 7), which was identified in the millipede Parafontaria laminata armigera , had an antiproliferative effect on the melanoma cells. This compound suppressed the activation of the focal adhesion kinase (FAK)-Akt pathway as well as the activation of extracellular signal-regulated kinase (Erk)1/2 pathway involved in cell proliferation. Expression of the cell cycle proteins, cyclin D1 and CDK4, was suppressed by glycosphingolipid 7. From these results, glycosphingolipid 7 suppressed the activation of the FAK-Akt pathway and of Erk1/2, which resulted in a decrease in the expression of cyclin D1 and CDK4. Glycosphingolipid 7 might be a candidate for an inhibitor of cell proliferation in melanomas.
关键词：glycosphingolipid;focal adhesion kinase;extracellular signal-regulated kinase;melanoma;proliferation