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Novel galectin-8 targeting polysaccharides from Scutellaria baicalensis: Characterization and anti-gastric
Jingyu Ye1, Guanyu Li2, Liushaoqiu Zhou2
1Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, 563006, China; Guizhou Aerospace Hospital, Zunyi, 563000, China.
Abstract:
Currently, galectin-8 has been demonstrated to enhance the proliferation of gastric cancer cells by activating the Ras signaling pathway, indicating its potential as a therapeutic target for gastric cancer. In this study, Scutellaria baicalensis acidic polysaccharide (SBP-A) was prepared and subsequently fractionated into three subfractions (SBP-A-1, SBP-A-2, and SBP-A-3) utilizing ion exchange chromatography. Subsequently, SBP-A-3 was further separated into SBP-A-3-1 and SBP-A-3-2 through the application of gel chromatography. Physicochemical analysis indicated that the compositions of SBP-A subfractions were mainly GalA, Rha, Gal, and Ara, with molecular weights varying from 2.7 kDa to 111.9 kDa. Fluorescence spectroscopy revealed that SBP-A-3-2 was identified as a glycan co-recognized by CRDs located at both termini of galectin-8. Moreover, anti-tumor experiments have demonstrated that SBP-A-3-2 exhibits the most pronounced inhibitory effect on the proliferation and migration of AGS cells, which is attributed to its affinity for galectin-8. The NMR analysis revealed that SBP-A-3-2 is a pectic polysaccharide with an HG domain and a minor proportion of RG-I domain in the main chain, along with trace amounts of trace →3,5)-α-Ara-(1 → and t-β-Gal neutral side chains. These findings provide valuable insights for studies of polysaccharides targeting galectin-8 for tumor treatment.
Insights
Scutellaria baicalensis acidic polysaccharide (SBP-A) fraction SBP-A-3-2 shows potent anti-gastric cancer activity by targeting galectin-8. This pectic polysaccharide inhibits cancer cell proliferation and migration, offering a novel therapeutic strategy.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Immunology
Background:
- Galectin-8 promotes gastric cancer cell proliferation via the Ras signaling pathway.
- Galectin-8 is a potential therapeutic target for gastric cancer treatment.
Purpose of the Study:
- To investigate the anti-tumor potential of Scutellaria baicalensis acidic polysaccharide (SBP-A) fractions against gastric cancer.
- To identify specific SBP-A fractions that interact with galectin-8 and inhibit cancer cell growth.
Main Methods:
- Preparation and fractionation of SBP-A using ion exchange and gel chromatography.
- Physicochemical characterization of SBP-A subfractions.
- Fluorescence spectroscopy to assess galectin-8 binding.
- In vitro anti-tumor assays on AGS gastric cancer cells.
- Nuclear Magnetic Resonance (NMR) analysis for structural elucidation.
Main Results:
- SBP-A was fractionated into SBP-A-1, SBP-A-2, and SBP-A-3, with SBP-A-3 further separated into SBP-A-3-1 and SBP-A-3-2.
- SBP-A-3-2, a pectic polysaccharide, demonstrated significant binding affinity to galectin-8.
- SBP-A-3-2 exhibited the strongest inhibition of AGS cell proliferation and migration.
- NMR analysis revealed SBP-A-3-2's structure as a pectic polysaccharide with HG and RG-I domains and specific neutral side chains.
Conclusions:
- SBP-A-3-2 is a novel galectin-8-binding polysaccharide with significant anti-gastric cancer properties.
- Targeting galectin-8 with SBP-A-3-2 represents a promising therapeutic approach for gastric cancer.
- Further research into SBP-A-3-2 could lead to new anti-cancer drug development.
