title: Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype.
abstract: Glioblastoma 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.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Nina
authors.initials: N
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd., Chengdu, Sichuan 610041, China.
authors.forename: Mengtian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd., Chengdu, Sichuan 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.affiliation: Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd., Chengdu, Sichuan 610041, China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd., Chengdu, Sichuan 610041, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Glioma, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D000067996:RAW 264.7 Cells; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D002726:Chlorogenic Acid