Faculty of Pharmacy, Keio University, 1–5–30 Shibakoen, Tokyo 105–8512, Japan.
Biol Pharm Bull. 2012;35(11):2054-8. doi: 10.1248/bpb.b12-00492. Epub 2012 Aug 20.
Endogenous sulfatide, such as 3-sulfated galactosylceramide (3-sulfatide) has been reported to be involved in neuronal development and regulation of tumor cell metastasis. Recently, a new 6-sulfated glucosylceramide (6-sulfatide) has been isolated from the ascidian, Ciona intestinalis. To determine the antitumor function of the new sulfatide, we examined the effects of synthetic 6-sulfatide and 3-sulfatide on the metastatic features of a murine melanoma cell line, B16F10. Both sulfatides significantly inhibited the adhesion of melanoma cells onto fibronectin-coated tissue plates and, the motility and invasion of the cells, with 6-sulfatide showing stronger inhibitory activities. In addition, both sulfatides inhibited α(5)-, and β(1)- but not α(v)- or β(3)-integrin expression. Furthermore, these sulfatides inhibited the activation of focal adhesion kinase, Akt, and extracellular signal-regulated kinase signaling pathways, which are thought to be important for cell migration and invasion. Therefore, these sulfatides may serve as promising drug candidates for the treatment of cancer metastasis.
内源性神经节苷脂,如 3-硫酸半乳糖基神经酰胺(3-硫酸苷脂)已被报道参与神经元发育和肿瘤细胞转移的调节。最近,一种新的 6-硫酸葡萄糖神经酰胺(6-硫酸苷脂)已从海鞘 Ciona intestinalis 中分离出来。为了确定新的神经节苷脂的抗肿瘤功能,我们研究了合成的 6-硫酸苷脂和 3-硫酸苷脂对鼠黑色素瘤细胞系 B16F10 的转移特征的影响。两种硫酸苷脂均显著抑制黑色素瘤细胞在纤维连接蛋白包被的组织板上的黏附,以及细胞的迁移和侵袭,6-硫酸苷脂显示出更强的抑制活性。此外,两种硫酸苷脂均抑制 α(5)-和 β(1)-整合素,但不抑制 α(v)-或 β(3)-整合素的表达。此外,这些硫酸苷脂抑制粘着斑激酶、Akt 和细胞外信号调节激酶信号通路的激活,这些通路被认为对细胞迁移和侵袭很重要。因此,这些硫酸苷脂可能成为治疗癌症转移的有前途的药物候选物。