Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/β-Catenin Pathway

Zhou, Zhaoyang; Wang, Yiqing; Ji, Rui; Zhang, Dekui; Ma, Chi; Ma, Wantong; Ma, Yunhao; Jiang, Xinrong; Du, Kangjia; Zhang, Rentao; Chen, Peng

doi:10.3389/fphar.2022.841918

Cited by 8 publications

(7 citation statements)

References 46 publications

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“…Additionally, other chemical components and their derivatives such as Emodin, Deoxyschizandrin A, Daucosterol, Chrysophanol, Vanillin, Caffeic acid, and Oleanolic acid have been reported to exhibit anti-CRC or anti-cancer effects in previous studies. [38–44] These results suggest that these components may play a crucial role in the therapeutic effectiveness of SJC in treating CRC and warrant further investigation.…”

Section: Discussionmentioning

confidence: 95%

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

Zheng,

Wang,

Gao

et al. 2023

Medicine

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While Salvia chinensis Benth (commonly known as “Shijianchuan” in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects.

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Section: Discussionmentioning

confidence: 95%

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

Zheng,

Wang,

Gao

et al. 2023

Medicine

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“…[76] The research team led by Professor Ma discovered that miR-149-3p downregulation in ETBF-treated cellular exosomes could accelerate Th17 cell differentiation and induce CRC, and that miR-149-3p downregulation by ETBF was reliant on METTL14-dependent m6A methylation. [77] In addition, Bacteroides fragilis enterotoxin can induce increased secretion of ROS by stimulating the production of spermine oxidase, a polyamine catabolic enzyme, in the IECs, leading Inhibiting colorectal cancer cell proliferation [98] Paris polyphylla Not mentioned Inhibiting the release of extracellular vesicles from F. nucleatum thereby preventing mitochondrial fusion and cell invasion in CRC cells [99] Vanillin derivatives Not mentioned Inhibiting F. nucleatum activity by increasing cell membrane permeability and disrupting bacterial integrity, suppressing the migration of HCT116 cells through downregulating the expression of E-cadherin and β-catenin [100] Oroxylin A Actinobacteria↓ Bacteroidetes↓ Proteobacteria↑ Firmicutes↑ Eubacterium coprostanoli-genes↑…”

Section: Short-chain Fatty Acids (Scfas) Inducing the Expansion Of Tr...mentioning

confidence: 99%

Visual analysis of colorectal cancer and gut microbiota: A bibliometric analysis from 2002 to 2022

Long,

Mao,

Zhang

et al. 2023

Medicine

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A growing number of studies have shown that gut microbiota (GM) plays an essential role in the occurrence and development of colorectal cancer (CRC). The current body of research exploring the relationship between CRC and GM is vast. Nevertheless, bibliometric studies in this area have not yet been reported. This study aimed to explore the hotspots and frontiers of research on GM and CRC in the past 20 years, which may provide a reference for researchers in this field. The Web of Science Core Collection database was searched for publications on CRC and GM from 2002 to 2022. The scientometric softwares CiteSpace and VOSviewer were used to visually analyze the countries, institutions, authors, journals, and keywords involved in the literature. Keywords co-occurrence, cluster, and burst analysis were utilized to further explore the current state and development trends of research on GM and CRC. A total of 2158 publications were included in this study, with a noticeably rising annual publication trend. The majority of these papers are from 80 nations, primarily China and the USA. J Yu was the most active author and WS Garrett has the highest citation. Among all institutions, Shanghai Jiao Tong University has the largest number of papers. Most of the publications were published in the International Journal of Molecular Sciences, with Science being the most frequently cited journal. The 4 main clusters mainly involved probiotics, inflammation, molecular mechanisms, and research methods. Current research hotspots included “Fusobacterium nucleatum,” “Escherichia coli,” etc. Newly emerging research has focused predominantly on immune response, gene expression, and recent strategies for the treatment of CRC with GM. The relationship between GM and CRC will continue to be a hot research area. Changes in the composition of GM in patients with CRC, the potential molecular mechanisms as well as probiotics and natural products used in the treatment of CRC have been the focus of current research and hotspots for future studies.

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“…Vascular endothelial-cadherin, a protein responsible for cell-cell junction at the endothelial level, was determined as the endothelial receptor for FadA. FadA co-localized with cadherin on endothelial cells caused the relocation of cadherin away from the cell-cell junctions [19]. As a result, endothelial permeability was increased by loss of the intercellular union, allowing the bacteria to cross the endothelium.…”

Section: Fusobacterium Nucleatummentioning

confidence: 99%

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer

et al. 2022

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There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pathogenic mechanisms of this relationship in a comprehensive manner. Finally, the main questions and further research perspectives are presented.

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Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/β-Catenin Pathway

Cited by 8 publications

References 46 publications

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study

Visual analysis of colorectal cancer and gut microbiota: A bibliometric analysis from 2002 to 2022

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer

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