Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity

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Authors
Jin, Weihua
He, Xinyue
Wu, Wanli
Bao, Yizhong
Wang, Sanying
Cai, Min
Zhang, Wenjing
Wang, Chunyu
Zhang, Fuming
Linhardt, Robert J.
Issue Date
2020-11-15
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
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.
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International Journal of Biological Macromolecules, 163, 776–787
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Full Citation
Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity, W. Jin, X. He, W. Wu, Y. Bao, S. Wang, M. Cai, W. Zhang, C. Wang, F. Zhang, R. J. Linhardt, G. Mao, W. Zhong, International Journal of Biological Macromolecules, 163, 776–787, 2020.
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18790003
1418130
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