College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Int J Biol Macromol. 2020 Nov 15;163:776-787. doi: 10.1016/j.ijbiomac.2020.07.069. Epub 2020 Jul 10.
Laminarin (LA), a storage glucan, was purified from the brown alga Sargassum thunbergii. After specific oxidation using the stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), together with NaBr and NaClO, glucoglucuronan (LAO) was obtained. Compositional analysis of LAO showed a molar ratio of glucuronic acid (GlcA) to glucose (Glc) of 12.7: 1. Nuclear magnetic resonance (NMR) and mass spectroscopy (MS) showed LAO to have a backbone of (1 → 3)-linked β-D-GlcpA interspersed with (1 → 3, 1 → 6)-linked β-D-Glcp, that was terminated with β-D-GlcpA. LAO inhibited human lung cancer A549 cell proliferation in vitro. IC values at 12 h and 24 h were 2.70 mg/mL and 2.85 mg/mL, respectively. Western blotting showed that TSC2 was up-regulated at an LAO concentration of 3.80 mg/mL. FAK, PI3K, P-AKT and mTOR were down-regulated, indicating LAO inhibited cancer cell proliferation through the FAK/PI3K/AKT/mTOR pathway. Surface plasmon resonance (SPR) studies revealed that LAO showed an IC of 0.07 mg/mL inhibiting the binding of heparin to fibroblast growth factor 1 (FGF1) LAO inhibition of heparin binding to FGF2 fluctuated between 15% and 28%, suggesting that LAO inhibits A549 cell proliferation by selectively interacting with FGF1.
从褐藻马尾藻中提取了一种储存性葡聚糖——昆布多糖（LA）。用稳定的氮氧自由基 2,2,6,6-四甲基哌啶-1-氧自由基（TEMPO）对其进行特定氧化后，与 NaBr 和 NaClO 一起得到了葡糖醛酸基葡聚糖（LAO）。LAO 的成分分析显示葡萄糖醛酸（GlcA）与葡萄糖（Glc）的摩尔比为 12.7:1。核磁共振（NMR）和质谱（MS）表明，LAO 的主链由（1 → 3）-连接的β-D-GlcpA 与（1 → 3,1 → 6）-连接的β-D-Glcp 交错组成，末端为β-D-GlcpA。LAO 在体外抑制人肺癌 A549 细胞增殖。12 h 和 24 h 的 IC 值分别为 2.70 mg/mL 和 2.85 mg/mL。Western blot 显示，LAO 在 3.80 mg/mL 浓度时 TSC2 上调。FAK、PI3K、P-AKT 和 mTOR 下调，表明 LAO 通过 FAK/PI3K/AKT/mTOR 通路抑制癌细胞增殖。表面等离子体共振（SPR）研究表明，LAO 对肝素与成纤维细胞生长因子 1（FGF1）结合的 IC 为 0.07 mg/mL。LAO 抑制肝素与 FGF2 结合的抑制率在 15%到 28%之间波动，这表明 LAO 通过选择性地与 FGF1 相互作用抑制 A549 细胞增殖。
