Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer

Oncotarget
Ting WuLiang Qiao

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.

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Citations

Jul 1, 2017·Archivum Immunologiae Et Therapiae Experimentalis·Katarzyna Sawa-Wejksza, Martyna Kandefer-Szerszeń
Apr 6, 2018·Future Medicinal Chemistry·Kirti S PrabhuShahab Uddin
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Feb 23, 2021·Oncotarget·Beatrice AraminiKhawaja Husnain Haider
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Nov 30, 2021·Journal of Biochemical and Molecular Toxicology·Uzini Devi DaimaryAjaikumar B Kunnumakkara

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