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Anti-cancer effect of dung beetle glycosaminoglycans on melanoma
- Source :
- BMC Cancer, BMC Cancer, Vol 19, Iss 1, Pp 1-12 (2019)
- Publication Year :
- 2018
-
Abstract
- Background Dung beetle glycosaminoglycan is known to possess anti-aging activities. However, its anti-cancer mechanisms are not fully elucidated yet. The objective of this study was to evaluate the anti-cancer effect of insect-derived polymer dung beetle glycosaminoglycan (GAG) after intraperitoneally injecting it to melanoma mice induced by B16F10 cells. Methods To determine molecular mechanism involved in the anti-cancer effect of dung beetle GAG, its origin N-glycan under 3KD Dalton was assayed for melanoma cell cytotoxicity. Quantitative comparisons of adhesive molecule on extracellular matrix and activities of tissue inhibitor of metalloprotease 2 (TIMP-2) were also investigated. In vivo anti-cancer effect of dung beetle GAG on solid tumor size, survival time and gene-expression profiles was also assayed using B10F10 melanoma mice model. Mice with induced melanoma were then treated with Catharsius molossus (dung beetle) GAG (CaG) at 5 mg/kg for 8 weeks to investigate its anti-cancer effects compared to bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG) and Huechys sanguinea glycosaminoglycan (HEG). Results These N-glycans derived from these GAG were composed of many linear heparinoid polysaccharides, polymers with hexose and N-acetylhexose. Adminstration with these GAGs increased survival time and decreased melanoma sizes in mice, in accordance with their inhibitory effects on cell growth ratio of melanoma B16F10. In addition, treatment with N-glycans derived from theses glycosaminoglycan increased activities of TIMP-2 in HMVEC cells pretreated with TNF-alpha and in melanoma cells, suggesting that they had anti-inflammatory and anticancer activities. In DNA microarray results, compared to control, CaG treated mouse group showed upregulation of 192 genes including collagen,typeI,alpha1 (Col1a1), consistent with the highly increased in vitro extracellular matrix (ECM) adhesion on collagen 1 and up-regulation of heparanase (Hpse). After treatment with CaG, a total of 152 genes were down-regulated, including nuclear RNA export factor (Nxf3) and hyaluronan proteoglycan link protein1 (Hapln1). Conclusions Glycosaminoglycan, CaG can strengthen ECM by increasing activity of TIMP-2 and adhesion activity on collagen known to inhibit changes of ECM, leading to tumor cell invasion and progression. Electronic supplementary material The online version of this article (10.1186/s12885-018-5202-z) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Cancer Research
Melanoma, Experimental
Queen of B. ignitus
Microarray
lcsh:RC254-282
Collagen Type I
Glycosaminoglycan
Extracellular matrix
03 medical and health sciences
Mice
0302 clinical medicine
Genetics
medicine
Animals
Humans
Catharsius molossus
Heparanase
Neoplasm Invasiveness
Cell Proliferation
Glucuronidase
Glycosaminoglycans
Oligonucleotide Array Sequence Analysis
Anti-cancer effect
Extracellular Matrix Proteins
Tissue Inhibitor of Metalloproteinase-2
biology
Cell growth
Chemistry
Melanoma
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
biology.organism_classification
medicine.disease
Molecular biology
Extracellular Matrix
Coleoptera
Collagen Type I, alpha 1 Chain
Gene Expression Regulation, Neoplastic
Collagen, type I, alpha 1
030104 developmental biology
Oncology
Proteoglycan
030220 oncology & carcinogenesis
biology.protein
Proteoglycans
Research Article
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC cancer
- Accession number :
- edsair.doi.dedup.....4951eb07d8ac7a199f9c840bf9e079b0