4.7 Article

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

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 140, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111542

Keywords

Melanoma; Icariside I; Gut microbiota; Systematic immunity; Metabolomics

Funding

  1. National Key Research and Development Project [2018YFE0110800]
  2. Foshan Core Technology Tackling Key Project [1920001000262]
  3. China Postdoctoral Science Foundation [2019M662893]
  4. National Natural Science Foundation of China [21635006]

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Recent studies show that icariside I, a novel anticancer agent, inhibits melanoma growth by modulating gut microbiota and host immunity, improving microbiota community structure and levels of microbiota-derived metabolites, leading to immune regulation and potential development as an anticancer drug.
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 anticancer 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.

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