Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and Stimulating Anoikis
| Autor: | Shan Kuang, Ge Liu, Weihua Jin, Ruobing Cao, Ju Wang, Chaomin Sun, Yeqi Shan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aquatic Organisms Lung Neoplasms Cell Pharmaceutical Science Mice 0302 clinical medicine Tubulin anoikis Carcinoma Non-Small-Cell Lung Drug Discovery Anoikis Phosphorylation Pharmacology Toxicology and Pharmaceutics (miscellaneous) lcsh:QH301-705.5 Mice Inbred BALB C Chemistry Polysaccharides Bacterial Cell biology adhesion medicine.anatomical_structure 030220 oncology & carcinogenesis Female Signal Transduction Down-Regulation Mice Nude Antineoplastic Agents Article 03 medical and health sciences Cell Line Tumor medicine Cell Adhesion Animals Humans cancer filiform structures Cell adhesion Protein kinase B Cell Proliferation A549 cell Pacific Ocean Bacteria Dose-Response Relationship Drug Cell growth Bacterial polysaccharide Xenograft Model Antitumor Assays βIII-tubulin 030104 developmental biology lcsh:Biology (General) polysaccharide Cancer cell Drug Screening Assays Antitumor Proto-Oncogene Proteins c-akt |
| Zdroj: | Marine Drugs Marine Drugs, Vol 16, Iss 3, p 85 (2018) Marine Drugs; Volume 16; Issue 3; Pages: 85 |
| ISSN: | 1660-3397 |
| Popis: | Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 inhibits the expression of βIII-tubulin in both transcription and translation levels; and (ii) EPS11 treatment dramatically decreases the phosphorylation of protein kinase B (PKB or AKT), a critical downstream effector of βIII-tubulin. Importantly, EPS11 evidently inhibits the growth of A549-derived tumor xenografts in vivo. Thus, our results suggest that EPS11 may be a potential candidate for human non-small cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis. |
| Databáze: | OpenAIRE |
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