Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
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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.
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.;
International Journal of Biological Macromolecules, 163, 776–787; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; International Journal of Biological Macromolecules; https://harc.rpi.edu/;