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Molecular mechanism of Antrodia cinnamomea sulfated polysaccharide on the suppression of lung cancer cell growth and migration via induction of transforming growth factor β receptor degradation.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2017 Feb; Vol. 95, pp. 1144-1152. Date of Electronic Publication: 2016 Nov 04. - Publication Year :
- 2017
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Abstract
- A sulfated polysaccharide of edible mushroom Antrodia cinnamomea (SPS) has been identified as a novel immunomodulatory agent. We examined the anti-cancer effects of SPS by conducting a series of in vitro studies. We found that SPS inhibits the growth of A549 and LLC1 lung cancer cells via the induction of cell cycle arrest and activation of caspase 3 and PARP. By contrast, we found that a non-sulfated polysaccharide of A. cinnamomea (NSPS) does not inhibit lung cancer cell viability. Moreover, NSPS does not induce changes in cell cycle distribution or activate apoptosis-related molecules in both A549 and LLC1 cells. High expression of transforming growth factor β (TGFβ) and TGFβ receptors (TGFRs) is correlated with lung tumorigenesis. SPS suppresses TGFβ-induced intracellular signaling events, including phosphorylation of Smad2/3, FAK, Akt, and cell migration. By contrast, non-sulfated polysaccharide (NSPS) does not exhibit the similar biological functions in both A549 and LLC1 cells. Mechanistically, we demonstrated SPS effectively reduces TGFR protein levels via induction of proteasome-dependent degradation pathway. Our study is the first to identify the pivotal role of SPS in the induction of TGFR degradation and activation of Caspase 3 and PARP, which leads to suppress viability and migration of lung cancer cells.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Antineoplastic Agents isolation & purification
Caspase 3 genetics
Caspase 3 metabolism
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Epithelial Cells metabolism
Epithelial Cells pathology
Focal Adhesion Kinase 1 genetics
Focal Adhesion Kinase 1 metabolism
Fruiting Bodies, Fungal chemistry
Fungal Polysaccharides isolation & purification
Humans
Immunologic Factors isolation & purification
Poly(ADP-ribose) Polymerases genetics
Poly(ADP-ribose) Polymerases metabolism
Proteasome Endopeptidase Complex metabolism
Proteolysis drug effects
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Receptors, Transforming Growth Factor beta genetics
Receptors, Transforming Growth Factor beta metabolism
Respiratory Mucosa drug effects
Respiratory Mucosa metabolism
Respiratory Mucosa pathology
Signal Transduction
Smad2 Protein genetics
Smad2 Protein metabolism
Smad3 Protein genetics
Smad3 Protein metabolism
Sulfates chemistry
Transforming Growth Factor beta genetics
Transforming Growth Factor beta metabolism
Antineoplastic Agents pharmacology
Antrodia chemistry
Epithelial Cells drug effects
Fungal Polysaccharides pharmacology
Gene Expression Regulation, Neoplastic
Immunologic Factors pharmacology
Proteasome Endopeptidase Complex drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 95
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 27818294
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2016.11.004