Analyses of the possible anti-tumor effect of yokukansan
The Kampo medicine yokukansan (YKS) has a wide variety of properties such as anxiolytic, anti-inflammatory and analgesic effects, and is also thought to regulate tumor suppression. In this study, we investigated the anti-tumor effect of YKS. We used Lewis lung carcinoma (LLC)-bearing mice that were fed food pellets containing YKS and then performed a fecal microbiota analysis, a microarray analysis for microRNAs (miRNAs) and an in vitro anti-tumor assay. The fecal microbiota analysis revealed that treatment with YKS partly reversed changes in the microbiota composition due to LLC implantation. Furthermore, a miRNA array analysis using blood serum showed that treatment with YKS restored the levels of miR-133a-3p/133b-3p, miR-1a-3p and miR-342-3p following LLC implantation to normal levels. A TargetScan analysis revealed that the epidermal growth factor receptor 1 signaling pathway is one of the major target pathways for these miRNAs. Furthermore, treatment with YKS restored the levels of miR-200b-3p and miR-200c-3p, a recognized mediator of cancer progression and controller of emotion, in the hypothalamus of mice bearing LLC. An in vitro assay revealed that a mixture of pachymic acid, saikosaponins a and d and isoliquiritigenin, which are all contained in YKS, exerted direct and additive anti-tumor effects. The present findings constitute novel evidence that YKS may exert an anti-tumor effect by reversing changes in the fecal microbiota and miRNAs circulating in the blood serum and hypothalamus, and the compounds found in YKS could have direct and additive anti-tumor effects.
KeywordsYokukansan Tumor MicroRNA Microbiota Hypothalamus
Cytotoxic T lymphocyte-associated protein 4
Epidermal growth factor receptor
Lewis lung carcinoma
Non-small cell lung cancer
We thank H. Kazamatsuri, M. Nakahama, W. Eguchi, and J.L. Waddington for their support. This work was supported by grants from MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan)-Supported Program for the Strategic Research Foundation at Private Universities, 2014–2018, S1411019.
Minoru N designed the research. CH, YH, TK, NK, KA, HM and Michiko N performed experiments. YH, TK, KA, HM and KI analyzed the data. HK, NK, Michiko N and Minoru N supervised the research. CH, MK and Minoru N wrote the paper.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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