Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype
0301 basic medicine
0303 health sciences
Macrophages
Antineoplastic Agents
Cell Differentiation
Article
Coculture Techniques
3. Good health
Disease Models, Animal
Mice
03 medical and health sciences
Phenotype
RAW 264.7 Cells
Treatment Outcome
13. Climate action
Cell Line, Tumor
Animals
Heterografts
Humans
Immunologic Factors
Chlorogenic Acid
Glioblastoma
Neoplasm Transplantation
DOI:
10.1038/srep39011
Publication Date:
2017-01-03T11:33:18Z
AUTHORS (13)
ABSTRACT
AbstractGlioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage.
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