Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

• DOI: 10.1038/srep39011
• Publication Date: 2017-01-03T11:33:18Z
• Authors: Nina Xue; Qin Zhou; Ming Ji; Jing Jin; Fangfang Lai; Ju Chen; Mengtian Zhang; Jing Jia; Huarong Yang; Jie Zhang; Wenbin Li; Jiandong Jiang; Xiaoguang Chen
• Keywords: CD11c; M2 Macrophage; Macrophage polarization; Tumor-associated macrophage; STAT6

Abstract Glioblastoma is an aggressive tumor that associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound low molecular weight, has anti-tumor effect in multiple malignant tumors. In the present study, we focused on macrophage polarization to investigate mechanisms behind anti-glioma response of CHA vitro and vivo . We found treatment increased expression M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) CD11c, reduced M2 Arg CD206 IL-4, resulting promoting production apoptotic-like cancer cells inhibiting growth co-culture experiments. The activations STAT1 STAT6, which are two crucial signaling events M2-polarization, were significantly promoted suppressed macrophages, respectively. Furthermore, G422 xenograft mice, proportion CD11c-positive macrophages decreased distribution CD206-positive tissue, consistent reduction weight observed CHA-treated mice. Overall these findings indicated as potential therapeutic approach reduce glioma through M1-polarized phenotypic macrophage.