6-Gingerol as an arginase inhibitor prevents urethane-induced lung carcinogenesis by reprogramming tumor supporting M2 macrophages to M1 phenotype

Food & Function
Jingjing YaoGangjun Du

Abstract

6-Gingerol (6-G) is the main bioactive component in Ginger (Zingiber officinale Roscoe). The aim of this study was to explore the contribution of macrophage polarization in 6-G-associated anti-cancer effects. In a urethane-induced lung carcinogenic model, lung carcinogenesis was positively correlated with macrophage (F4/80+) infiltration in lung interstitial in the control group. Furthermore, higher numbers of arginase+/F4/80+ M2 cells than iNOS+/F4/80+ M1 cells were observed in interstitial macrophages. Moreover, macrophage depletion by liposome-encapsulated clodronate (LEC) could significantly prevent lung carcinogenesis, whereas pexidartinib promoted lung carcinogenesis. After 6-G treatment, lung carcinogenesis was ameliorated with increased M1 macrophages and decreased M2 macrophages in the lung interstitial. ELISA showed that the levels of IFN-γ and IL-12 increased and the levels of IL-10 and TGF-β1 decreased in the alveolar cavity compared to those in the control group. Unexpectedly, the carcinogenesis-preventing efficacy of 6-G was promoted in LEC-treated mice, but completely aborted in pexidartinib-treated mice. In the in vitro experiment, 6-G reset the IL-4-induced arginase+ M2 cells toward iNOS+ M1 cells and exhibited...Continue Reading

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Citations

Jun 22, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Qi RenChangjie Ren
Oct 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi Shin EngJung San Chang
Nov 22, 2019·Anti-cancer Agents in Medicinal Chemistry·Rumana AhmadArvind K Srivastava
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Zhen WeiPing Yi
Jul 27, 2021·International Reviews of Immunology·Hai-Cun ZhouHong-Bin Liu
Apr 20, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Rosália Maria Tôrres de LimaAna Amélia de Carvalho Melo Cavalcante

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Methods Mentioned

BETA
ELISA
nitric oxide assay
electrophoresis

Software Mentioned

GraphPad Prism
ImageJ

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