Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota

被引:60
作者
Gong, Yanling [1 ]
Dong, Rong [1 ,2 ]
Gao, Xiaomeng [1 ]
Li, Jin [1 ]
Jiang, Li [1 ]
Zheng, Jiale [1 ]
Cui, Sunliang [3 ]
Ying, Meidan [1 ]
Yang, Bo [1 ]
Cao, Ji [1 ]
He, Qiaojun [1 ]
机构
[1] Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Inst Pharmacol & Toxicol, Hangzhou, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hangzhou Peoples Hosp 1, Hangzhou, Zhejiang, Peoples R China
[3] Zhejiang Univ, Coll Pharmaceut Sci, Inst Drug Discovery & Design, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Neohesperidin; APC min/ plus transgenic mice; Gut microbiota; Colorectal cancer; Cancer prevention; CANCER; COLON; INFLAMMATION; ANTICANCER; GENETICS; MODEL;
D O I
10.1016/j.phrs.2019.104460
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC(min/+) transgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.
引用
收藏
页数:11
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