G.B Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia.
G.B Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia.
Int J Biol Macromol. 2017 Nov;104(Pt A):508-514. doi: 10.1016/j.ijbiomac.2017.06.074. Epub 2017 Jun 19.
Marine organisms are rich sources of lectins. Lectins are able to bind specifically and reversibly to different types of carbohydrates or glycoproteins. The present study reports the evaluation of glycan binding profile and anti-tumor potential of lectin CGL from the sea mussel Crenomytilus grayanus. Glycan array assay revealed that CGL was able to bind both α and β anomer of galactose, but interaction with the αGal-terminated glycans was stronger. Analysis of most common glycan motifs for CGL showed high affinity to Galα1-4Galβ1-4GlcNAc motif similar to globotriose structure (Gb3: Galα1-4Galβ1-4Glc), the epitope of globotriaosylceramide. CGL recognized Gb3 on the surface of Burkitt's lymphoma Raji cells (high Gb3 expression), leading to dose-dependent cytotoxic effect, G2/M phase cell cycle arrest and apoptosis. Lectin had no effect on erythroleukemia K562 cells (no Gb3 expression). The activity of CGL was specifically blocked by α-galactoside. Our findings suggest the use of CGL in cancer diagnosis and treatment.
海洋生物是凝集素的丰富来源。凝集素能够特异性和可逆地结合不同类型的碳水化合物或糖蛋白。本研究报告了来自贻贝 Crenomytilus grayanus 的凝集素 CGL 的糖结合谱和抗肿瘤潜力的评估。糖基阵列分析显示，CGL 能够结合半乳糖的 α 和 β 异构体，但与 αGal 末端聚糖的相互作用更强。对 CGL 最常见糖基基序的分析表明，它与类似Globotriose 结构（Gb3：Galα1-4Galβ1-4Glc）的 Galα1-4Galβ1-4GlcNAc 基序具有高亲和力，这是神经节苷脂 Gb3 的表位。CGL 识别伯基特淋巴瘤 Raji 细胞（高 Gb3 表达）表面的 Gb3，导致剂量依赖性细胞毒性作用、G2/M 期细胞周期停滞和细胞凋亡。凝集素对红白血病 K562 细胞（无 Gb3 表达）没有影响。CGL 的活性被α-半乳糖苷特异性阻断。我们的研究结果表明 CGL 可用于癌症诊断和治疗。
