title: Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer.
abstract: Macrophages are a major component of inflammatory and tumor microenvironment. We previously reported that embelin suppresses colitis-associated tumorigenesis. Here, the role of macrophage targeting in the anti-inflammatory and anti-tumor properties of embelin was investigated. By using colitis-associated cancer (CAC) model, we demonstrated that embelin significantly depleted colon macrophages by blocking their recruitment. Moreover, embelin attenuated M2-like polarization of macrophages within the tumor microenvironment and eliminated their tumor-promoting functions during the development of CAC. Embelin potently inhibited NF-κB signaling in macrophages and decreased the production of key pro-inflammatory cytokines and tumorigenic factors involved in CAC, such as TNFα, IL-6 and COX-2. In addition, embelin directly reduced the polarization of M2 macrophages in vitro even in the presence of Th2 cytokines. These results suggested that targeting macrophages is, at least in part, responsible for the anti-tumor activity of embelin in CAC. Our observations strengthen the rationale for future validation of embelin in the prevention and treatment of CAC.
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Guigen
authors.initials: G
authors.lastname: Teng
authors.affiliation: Department of Gerontology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shuai
authors.affiliation: Research Center of Basic Medical Sciences and Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003092:Colitis / Q000150:complications*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016227:Benzoquinones; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C010945:embelin
keywords: colitis-associated cancer; embelin; macrophage; target therapy