scholarly journals Inhibitory Effects of Apigenin on Tumor Carcinogenesis by Altering the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shichang Bian ◽  
Hongjuan Wan ◽  
Xinyan Liao ◽  
Weisheng Wang
Keyword(s):  
Colon Cancer ◽  
Treatment Group ◽  
16S Rrna ◽  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Potential Mechanism ◽  
Inhibitory Effects ◽  
Antitumor Effects

The flavonoid apigenin is common to many plants. Although the responsible mechanisms have yet to be elucidated, apigenin demonstrates tumor suppression in vitro and in vivo. This study uses an azoxymethane (AOM)/dextran sodium sulfate- (DSS-) induced colon cancer mouse model to investigate apigenin’s potential mechanism of action exerted through its effects upon gut microbiota. The size and quantity of tumors were reduced significantly in the apigenin treatment group. Using 16S rRNA high-throughput sequencing of fecal samples, the composition of gut microbiota was significantly affected by apigenin. Further experiments in which gut microbiota were reduced and feces were transplanted provided further evidence of apigenin-modulated gut microbiota exerting antitumor effects. Apigenin was unable to reduce the number or size of tumors when gut microbiota were depleted. Moreover, tumor inhibition effects were initiated following the transplant of feces from mice treated with apigenin. Our findings suggest that the effect of apigenin on the composition of gut microbiota can suppress tumors.

scholarly journals Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand

2020 ◽  
Author(s):  
Junhui Yu ◽  
Kui Yang ◽  
Jianbao Zheng ◽  
Wei Zhao ◽  
Xuejun Sun
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Farnesoid X Receptor ◽  
Colon Cancer Cells ◽  
Antitumor Effects ◽  
Colorectal Tumorigenesis ◽  
Tumor Inhibition ◽  
Combination Study

Abstract The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC.

In vitro and in vivo inhibitory effects of a Pleurotus eryngii protein on colon cancer cells

2017 ◽  
Vol 8 (10) ◽  
pp. 3553-3562 ◽  
Author(s):  
Biao Yuan ◽  
Ning Ma ◽  
Liyan Zhao ◽  
Ermin Zhao ◽  
Zili Gao ◽  
...  
Keyword(s):  
Cell Culture ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pleurotus Eryngii ◽  
Colon Cancer Cells ◽  
Inhibitory Effects ◽  
Tumor Models

The inhibitory effects of a protein isolated from Pleurotus eryngii were demonstrated in both cell culture and mouse allograft tumor models.

scholarly journals Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Binbin Xie ◽  
Bingjun Bai ◽  
Yuzi Xu ◽  
Yunlong Liu ◽  
Yiming Lv ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tissue Sample ◽  
Suppressive Effect ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Antitumor Effects ◽  
Molecular Features ◽  
Induced Apoptosis

AbstractRight-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via β-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.

scholarly journals Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
You-Cai Yi ◽  
Rui Liang ◽  
Xiao-Yu Chen ◽  
Hui-Ning Fan ◽  
Ming Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Dna Synthesis ◽  
Specific Inhibitor ◽  
Inhibitory Effects ◽  
Antitumor Effects ◽  
Cycle Progression ◽  
Cycle Arrest

Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling.

scholarly journals Fenofibrate Exerts Antitumor Effects in Colon Cancer via Regulation of DNMT1 and CDKN2A

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Rui Kong ◽  
Nan Wang ◽  
Wei Han ◽  
Wen Bao ◽  
Jie Lu
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Therapy ◽  
Cell Cycle Distribution ◽  
Peroxisome Proliferator ◽  
Antitumor Effects ◽  
Mesenchymal Transition

Peroxisome proliferator-activated receptor alpha (PPARA) is the molecular target of fibrates commonly used to treat dyslipidemia and diabetes. Recently, the potential role of PPARA in other pathological conditions, such as cancers, has been recognized. Here, using bioinformatics analysis, we found that PPARA was expressed at relatively low levels in pancancers, and Kaplan-Meier analyses revealed that high PPARA protein expression was correlated with better survival of patients with colon cancer. In vitro experiments showed that fenofibrate regulated cell cycle distribution, promoted apoptosis, and suppressed cell proliferation and epithelial mesenchymal transition by activating PPARA. PPARA activation inhibited DNMT1 activity and abolished methylation-mediated CDKN2A repression. Downregulation of cyclin-CDK complexes led to the restoration of CDKN2A, which caused cell cycle arrest in the G1 phase via regulation of the CDKN2A/RB/E2F pathway. Finally, we demonstrated that fenofibrate administration inhibited tumor growth and DNMT1 activity in vivo. The PPARA agonist, fenofibrate, might serve as an applicable agent for epigenetic therapy of colon cancer patients.

scholarly journals Potential of phenolic compounds and their gut microbiota-derived metabolites to reduce microbial TMA formation: Application of an in vitro fermentation high throughput screening model

2022 ◽  
Author(s):  
Lisard Iglesias-Carres ◽  
Emily Krueger ◽  
Jacob Herring ◽  
Jeffery Tessem ◽  
Andrew Neilson
Keyword(s):  
Gut Microbiota ◽  
Caffeic Acid ◽  
High Throughput Screening ◽  
Ex Vivo ◽  
Inhibitory Effects ◽  
In Vitro Fermentation ◽  
Choline Metabolism ◽  
Fermentation Model

Trimethylamine N-oxide (TMAO) is a pro-atherosclerotic product of dietary choline metabolism generated by a microbiome-host axis. The first step in this pathway is enzymatic metabolism of choline to trimethylamine (TMA) by the gut microbiota. This reaction could be targeted to reduce atherosclerosis risk. We aimed to evaluate potential inhibitory effects of select dietary phenolics and their relevant gut microbial metabolites on TMA production via a human ex vivo-in vitro fermentation model. Various phenolics inhibited choline use and TMA production. The most bioactive compounds tested (caffeic acid, catechin and epicatechin) reduced TMA-d9 formation (compared to control) by 57.5 ± 1.3% to 72.5 ± 0.4% at 8 h and preserved remaining choline-d9 concentrations by 194.1 ± 6.4% to 256.1 ± 6.3% compared to control conditions at 8 h. These inhibitory effects were achieved without altering cell respiration or cell growth. However, inhibitory effects decreased at late fermentation times, which suggest that these compounds delay choline metabolism rather than completely inhibiting TMA formation. Overall, caffeic acid, catechin and epicatechin were the most effective non-cytotoxic inhibitors of choline use and TMA production. Thus, these compounds are proposed as lead bioactives to test in vivo.

scholarly journals Potential of phenolic compounds and their gut microbiota-derived metabolites to reduce microbial TMA formation: Application of an in vitro fermentation high throughput screening model

2021 ◽  
Author(s):  
Lisard Iglesias-Carres ◽  
Emily Krueger ◽  
Jacob Herring ◽  
Jeffery Tessem ◽  
Andrew Neilson
Keyword(s):  
Gut Microbiota ◽  
High Throughput Screening ◽  
Ex Vivo ◽  
Inhibitory Effects ◽  
In Vitro Fermentation ◽  
Choline Metabolism ◽  
Fermentation Model ◽  
Dietary Choline

Trimethylamine N-oxide (TMAO) is a pro-atherosclerotic product of dietary choline metabolism generated by a microbiome-host axis. The first step in this pathway is enzymatic metabolism of choline to trimethylamine (TMA) by the gut microbiota. This reaction could be targeted to reduce atherosclerosis risk. We aimed to evaluate potential inhibitory effects of select dietary phenolics and their relevant gut microbial metabolites on TMA production via a human ex vivo-in vitro fermentation model. Various phenolics inhibited choline use and TMA production, especially larger compounds or their larger metabolites, without altering cell respiration or cell growth. However, inhibitory effects decreased at late fermentation times, which suggest that these compounds delay choline metabolism rather than completely inhibiting TMA formation. Overall, caffeic acid, catechin and epicatechin were the most effective non-cytotoxic inhibitors of choline use and TMA production. Thus, these compounds are proposed as lead bioactives to test in vivo.

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