Microbiome analysis combined with targeted metabolomics reveal immunological anti-tumor activity of icariside I in a melanoma mouse model

Recent studies report that the gut microbiome can enhance systemic and antitumor immunity by modulating responses to antibody immunotherapy in melanoma patients. In this study, we found that icariside I, a novel anti-cancer agent isolated from Epimedium, significantly inhibited B16F10 melanoma growt...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2021-08, Vol.140, p.111542, Article 111542
Main Authors: Chen, Gui, Cao, Zheng, Shi, Zunji, Lei, Hehua, Chen, Chuan, Yuan, Peihong, Wu, Fang, Liu, Caixiang, Dong, Manyuan, Song, Yuchen, Zhou, Jinlin, Lu, Yujing, Zhang, Limin
Format: Article
Language:English
Subjects:
Gut microbiota
Icariside I
Melanoma
Metabolomics
Systematic immunity
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Summary:Recent studies report that the gut microbiome can enhance systemic and antitumor immunity by modulating responses to antibody immunotherapy in melanoma patients. In this study, we found that icariside I, a novel anti-cancer agent isolated from Epimedium, significantly inhibited B16F10 melanoma growth in vivo through regulation of gut microbiota and host immunity. Oral administration of icariside I improved the microbiota community structure with marked restoration of Lactobacillus spp. and Bifidobacterium spp. abundance in the cecal contents of tumor-bearing mice. We also found that icariside I improves the levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs) and indole derivatives, consequently promoting repair of the intestinal barrier and reducing systemic inflammation of tumor-bearing mice. Icariside I exhibited strong immunological anti-tumor activity, directly manifested by up-regulation of multiple lymphocyte subsets including CD4+ and CD8+ T cells or NK and NKT cells in peripheral blood of tumor-bearing mice. Collectively, these results suggest that icariside I, via its microbiome remodeling and host immune regulation properties, may be developed as an anticancer drug. •Icariside I inhibits melanoma growth in B16F10-xenograft model.•Icariside I improves intestinal gut microbiota and its metabolites.•Icariside I improves host immunity for inhibition of tumor growth.•Enhanced host immunity positively correlated with gut microbiota and its metabolites.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2021.111542