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A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
- Source :
- Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules; Volume 22; Issue 3; Pages: 384, Molecules, Vol 22, Iss 3, p 384 (2017)
- Publication Year :
- 2017
- Publisher :
- MDPI, 2017.
-
Abstract
- Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their biological activities have been carried out. However, little is known regarding the antitumor properties of polysaccharides from B. exarata, hence the polysaccharides from B. exarata have been investigated here. One polysaccharide conjugate BEPS-IA was isolated and purified from B. exarata. It mainly consisted of mannose and glucose in a molar ratio of 1:2, with an average molecular weight of 127 kDa. Thirteen general amino acids were identified to be components of the protein-bound polysaccharide. Methylation and NMR studies revealed that BEPS-IA is a heteropolysaccharide consisting of 1,4-linked-α-d-Glc, 1,6-linked-α-d-Man, 1,3,6-linked-α-d-Man, and 1-linked-α-d-Man residue, in a molar ratio of 6:1:1:1. In order to test the antitumor activity of BEPS-IA, we investigated its effect against the growth of human hepatocellular carcinoma cells HepG2 in vitro. The result showed that BEPS-IA dose-dependently exhibited an effective HepG2 cells growth inhibition with an IC50 of 112.4 μg/mL. Flow cytometry analysis showed that BEPS-IA increased the populations of both apoptotic sub-G1 and G1 phase. The result obtained from TUNEL assay corroborated apoptosis which was shown in flow cytometry. Western blot analysis suggested that BEPS-IA induced apoptosis and growth inhibition were associated with up-regulation of p53, p21 and Bax, down-regulation of Bcl-2. These findings suggest that BEPS-IA may serve as a potential novel dietary agent for hepatocellular carcinoma.
- Subjects :
- Gastropoda
Pharmaceutical Science
Microscopy, Atomic Force
Analytical Chemistry
chemistry.chemical_compound
Drug Discovery
Amino Acids
bcl-2-Associated X Protein
chemistry.chemical_classification
medicine.diagnostic_test
Liver Neoplasms
apoptosis
04 agricultural and veterinary sciences
Hep G2 Cells
040401 food science
Biochemistry
Proto-Oncogene Proteins c-bcl-2
Chemistry (miscellaneous)
Molecular Medicine
Growth inhibition
human hepatocellular carcinoma HepG2 cells
Carcinoma, Hepatocellular
Normal diet
Bullacta exarata
Antineoplastic Agents
Biology
Oncogene Protein p21(ras)
polysaccharide
Polysaccharide
Methylation
Article
Flow cytometry
lcsh:QD241-441
0404 agricultural biotechnology
lcsh:Organic chemistry
Western blot
Polysaccharides
medicine
Animals
Humans
Physical and Theoretical Chemistry
IC50
Cell Proliferation
Spectrum Analysis
Organic Chemistry
biology.organism_classification
Molecular biology
G1 Phase Cell Cycle Checkpoints
In vitro
chemistry
Tumor Suppressor Protein p53
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 22
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Accession number :
- edsair.doi.dedup.....97f4d91b4d3b4a3bec8baecc58659217