BIOLOGICAL TRACE ELEMENT RESEARCH
·
2023
·
IF 3.9
Cui Jinling,Li Jingsi,Zhao Shuang,Fan Lihong,Yin Shutao,Zhao Chong,Hu Hongbo
Drug combination is considered to be an effective approach to improve the efficacy of cancer therapy and chemoprevention. Selenite, a representative of inorganic form of selenium, and butyrate, a major short-chain fatty acid, are two well-documented colon cancer dietary chemopreventive agents with distinct molecular mechanisms. We hypothesized that combination of selenite and butyrate might produce improved outcome against colon cancer. This hypothesis was tested using both HCT116 human colon cancer cells and its xenograft mouse model in the present study. The in vitro study showed a synergistically inhibitory effect on HCT116 colon cancer cells but not on NCM460 normal human colon mucosal epithelial cells. Consistent with the in vitro study, results of the xenograft mouse model further demonstrated that combination of selenite and butyrate led to improved efficacy in comparison with each agent alone. Mechanistically, the induction of alanine-serine-cysteine transporter 2 (ASCT2) by selenite repressed its inhibitory effect on colon cancer cells, which was reversed by its co-treatment with butyrate. The findings of the present study denote the likely potential for developing selenite/butyrate combination remedy to combat against colon cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 11
·9634-9650
·
IF 4.171
Jie Shen,Pei Li,Shuangshuang Liu,Qing Liu,Yue Li,Zheng Zhang,Chengmin Yang,Mengying Hu,Yuhua Sun,Chunnian He,Peigen Xiao
Despite that colorectal cancer (CRC) is a severe global health problem, effective chemopreventive strategies against CRC are still lacking. Huang-qin tea (HQT), a healthy herbal tea, is prepared from the aerial parts of Scutellaria baicalensis Georgi and has been consumed in China for thousands of years. HQT contains abundant flavonoids, which display potent anticancer effects, but no research studies have investigated the cancer-preventive effects of HQT on CRC in vivo. Here, we found that HQT inhibits azoxymethane-induced aberrant crypt foci (ACF) formation in a preneoplastic colonic ACF rat model. The essential role of the gut microbiota in the chemopreventive effect of HQT on CRC in a pseudo-germ-free rat model was confirmed. Besides, HQT modulates inflammatory cytokine expression by significantly decreasing IL-1β, IL-6, IL-10, and TNF-α expression, and elevating IFN-γ production. 16S rDNA sequencing analysis indicated that HQT regulated the gut microbiota by increasing the abundance of beneficial bacteria (Lachnoclostridium, Alistipes, Roseburia, and Lactococcus) and reducing the levels of Bacteroides, Parasutterella, and unidentified_Clostridiales. Fecal metabolomics showed that HQT modulated the AOM-induced metabolomic disorder, and these altered metabolites were almost involved in the lipid metabolic pathways. The Spearman correlation analysis revealed a correlation between the gut microbiota and fecal metabolites. Collectively, these results suggested that HQT exerted beneficial effects on host health by inhibiting inflammation, and by regulating the gut microbiota profile and certain metabolic pathways. In conclusion, HQT inhibits AOM-induced ACF formation by modulating the gut microbiota composition and improving metabolomic disorders, indicating the potential of HQT as a functional beverage candidate for the prevention and treatment of CRC.
研究领域:
肿瘤学
·
药理学
·
微生物学
·
代谢组学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2016
·Vol. 12
·期 19
·2595-2608
·
IF 8.315
Yu Gao,Songen Gu,Yingying Zhang,Xiaodong Xie,Ting Yu,Yusheng Lu,Yewei Zhu,Wenge Chen,Huijuan Zhang,Haiyan Dong,Patrick J. Sinko,Lee Jia
The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Microbiology
·
2023
·Vol. 8
·期 5
·919-933
·
IF 28.3
Han Ji-Xuan,Tao Zhi-Hang,Wang Ji-Lin,Zhang Lu,Yu Chen-Yang,Kang Zi-Ran,Xie Yuanhong,Li Jialu,Lu Shiyuan,Cui Yun,Xu Jia,Zhao Enhao,Wang Ming,Chen Jinxian,Wang Zheng,Liu Qiang,Chen Hui-Min,Su Wenyu,Zou Tian-Hui,Zhou Cheng-Bei,Hong Jie,Chen Haoyan,Xiong Hua,Chen Ying-Xuan,Fang Jing-Yuan
Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.
研究领域:
肿瘤学
·
胃肠病学
·
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CEREAL SCIENCE
·
2022
·
IF 4.075
Liping Ye,Wenquan Huang,Yuehua Deng,Zhiqiang Li,Yanbin Jiang,Qiuling Xie
Curcumin (Cur) has been widely studied for its chemo-preventive and chemotherapeutic effects against various types of human cancers, but the clinical application of curcumin is limited due to multiple delivery challenges, including poor water solubility, poor membrane permeability and easy degradation under alkaline conditions. Zein is an excellent carrier for pharmaceutical preparations because of its non-toxicity and biodegradability, but the plant protein source and hydrophobicity limit the application of zein in biomedical applications. The aim of this study is to overcome the limitations of Cur and zein in clinical therapy. To improve the hydrophilicity of zein and obtain a highly stable drug delivery system (DDS), zein was modified with carboxylated pluronic to prepare pluronic-zein (ZSP). The results indicated that the ZSP prepared not only has good hydrophilic and dispersibility properties, where the surface contact angle of the ZSP prepared is reduced by 33.1%–62.8%, but also its stability is not affected by pH and salinity compared with zein particles. After loading Cur into ZSP particles, Cur-ZSP DDS with good dispersibility and drug loading was prepared. Cur-ZSP DDS exhibited sustained release in the simulated in vitro environment. Cell experiments showed that ZSP presented as non-toxic. After loading with Cur, the cytotoxicity of Cur-ZSP DDS was significantly higher than that of raw Cur. The results provide new insight into the construction of zein-based oral drug delivery systems.
研究领域:
药学
·
生物医学工程
·
药物递送系统
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）