Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity.
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. IC50 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 IC50 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.
['Jin|Weihua|W|', 'He|Xinyue|X|', 'Wu|Wanli|W|', 'Bao|Yizhong|Y|', 'Wang|Sanying|S|', 'Cai|Min|M|', 'Zhang|Wenjing|W|', 'Wang|Chunyu|C|', 'Zhang|Fuming|F|', 'Linhardt|Robert J|RJ|', 'Mao|Genxiang|G|', 'Zhong|Weihong|W|']
D000970:Antineoplastic Agents D014408:Biomarkers, Tumor D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D002851:Chromatography, High Pressure Liquid D005936:Glucans D020723:Glucuronic Acid D006801:Humans D009682:Magnetic Resonance Spectroscopy D013058:Mass Spectrometry D015394:Molecular Structure D015398:Signal Transduction
Glucoglucuronan Laminarin Anti-lung cancer activity