Structural characterization and anti-lung cancer activity of a sulfated glucurono-xylo-rhamnan from Enteromorpha prolifera

Weihua Jin; Xinyue He; Liufei Long; Qiufu Fang; Bin Wei; Jiadong Sun; Wenjing Zhang; Hong Wang; Fuming Zhang; Robert J Linhardt

doi:10.1016/j.carbpol.2020.116143

Structural characterization and anti-lung cancer activity of a sulfated glucurono-xylo-rhamnan from Enteromorpha prolifera

Carbohydr Polym. 2020 Jun 1:237:116143. doi: 10.1016/j.carbpol.2020.116143. Epub 2020 Mar 9.

Authors

Weihua Jin¹, Xinyue He², Liufei Long², Qiufu Fang², Bin Wei³, Jiadong Sun⁴, Wenjing Zhang⁵, Hong Wang³, Fuming Zhang⁶, Robert J Linhardt⁷

Affiliations

¹ 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. Electronic address: jinweihua@zjut.edu.cn.
² College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
³ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, China.
⁴ Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA; Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, 20878, USA.
⁵ Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
⁶ Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
⁷ Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biological Science, Departments of Chemistry and Chemical Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

PMID: 32241440
DOI: 10.1016/j.carbpol.2020.116143

Abstract

A sulfated glucurono-xylo-rhamnan (EP-3-H) was purified from a green alga, Enteromorpha prolifera. EP-3-H and its oligomers were characterized by high performance liquid chromatography, mass spectrometry and one and two-dimensional nuclear magnetic resource spectroscopy. The structural analysis showed EP-3-H has a backbone of glucurono-xylo-rhamnan, branches with glucuronic acid and sulfated at C3 of rhamnose and/or C2 of xylose. The inhibition of EP-3-H on human lung cancer A549 cell proliferation in vitro and its therapeutic effects in BALB/c-nu mice in vivo were determined to evaluate the anti-lung cancer activity of EP-3-H. The tumor inhibition level was 59 %, suggesting that EP-3-H might be a good candidate for the treatment of lung cancer. Surface plasmon resonance (SPR) studies revealed the IC₅₀ on the binding of fibroblast growth factors, (FGF1 and FGF2), to heparin were 0.85 and 1.47 mg/mL, respectively. These results suggest that EP-3-H inhibits cancer proliferation by interacting with these growth factors.

Keywords: Anti-lung cancer activity; Glucurono-xylo-rhamnan; Growth factor; Interaction; Surface plasmon resonance.

MeSH terms

A549 Cells
Animals
Antineoplastic Agents* / isolation & purification
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Cell Proliferation / drug effects
Deoxy Sugars* / isolation & purification
Deoxy Sugars* / pharmacology
Deoxy Sugars* / therapeutic use
Fibroblast Growth Factor 1 / metabolism
Fibroblast Growth Factor 2 / metabolism
Heparin / metabolism
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Male
Mannans* / isolation & purification
Mannans* / pharmacology
Mannans* / therapeutic use
Mice, Inbred BALB C
Mice, Nude
Sulfates
Ulva / chemistry

Substances

Antineoplastic Agents
Deoxy Sugars
Mannans
Sulfates
Fibroblast Growth Factor 2
Fibroblast Growth Factor 1
rhamnan
Heparin