Targeting of oncogenic signaling pathways by berberine for treatment of colorectal cancer

Hallajzadeh, Jamal; Dana, Parisa Maleki; Mobini, Moein; Asemi, Zatollah; Mansournia, Mohammad Alì; Sharifi, Mehran; Yousefi, Bahman

doi:10.1007/s12032-020-01367-9

Cited by 26 publications

(18 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, BBR is currently gaining more attention due to its promising therapeutic effects on colorectal cancer (CRC). Moreover, emerging evidence demonstrated that BBR suppressed colon tumorigenesis via controlling cell signaling pathways, inducing apoptosis, attenuating oxidative stress, and inhibiting inflammatory response (10). However, its clinical efficacy also hard to be explained entirely because its absolute bioavailability is very low (11).…”

Section: Introductionmentioning

confidence: 99%

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Chen

Zhang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis in AOM/DSS mice with or without BBR administration was measured. The composition and abundance of gut microbiota was investigated by using 16S rRNA. Meanwhile, feces samples were analyzed with 1 H NMR spectroscopy to investigate the metabolic alterations. As a result, BBR significantly reduced intestinal tumor development with lower macroscopic polyps and ki-67 expression of intestinal tissue, and better colonic morphology in mice. Moreover, BBR altered the composition of gut microbiota in AOM/DSS mice obviously, which were characterized by a decrease of Actinobacteria and Verrucomicrobia significantly at the phylum level. At the genus level, it was able to suppress pathogenic species, such as f_Erysipelotrichaceae, Alistipes, and elevate some short-chain fatty acids (SCFA)-producing bacteria, including Alloprevotella, Flavonifractor, and Oscillibacter. Metabolic data further revealed that BBR induced metabolic changes in feces focus on regulating glycometabolism, SCFA metabolism and amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are the products of interactions between the host and the microbial community. This study showed that BBR induced alterations in microbiota and metabolic in AOM/DSS mice, which might providing new insight into the inhibition effects of BBR on CRC.

show abstract

Section: Introductionmentioning

confidence: 99%

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Chen

Zhang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Chronic inflammation is one of the characteristics of CRC. In the microenvironment of CRC, dense infiltrate of immune cells stimulates the secretion of proinflammatory cytokines, such as interleukin-(IL-) 6, IL-8, IL-1β, and TNF-α, which can synergistically activate signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-B (NF-κB), and hypoxia-inducible factor 1α (HIF-1α) pathways, resulting in progression of CRC [44,45]. As a well-known transcription factor and tumor suppresser, p53 protein drive cell apoptosis to avoid possibly cancer-inducing damaged DNA passing on to daughter cells.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Core Chinese Herbs against Colorectal Cancer: A Study Based on Data Mining and Network Pharmacology

Lin

Liang

Peng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.

show abstract

“…Tumorigenesis is frequently accompanied by multiple genetic alterations at the transcription level (12). High metastasis rate of DPC after radical resection has made it a worldwide public health problem.…”

Section: Discussionmentioning

confidence: 99%

Identification of critical pathways and potential therapeutic targets in Poorly differentiated duodenal papilla adenocarcinoma

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets.Methods: Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs) and protein–protein interaction (PPI) network was constructed for functional modules analysis and dentification of hub genes. Results: A total of 110 DEGs were identified from our RNA-Seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out six hub genes including IL-6, LEP, LCN2, CCND1, FABP4 and MMP1, which were identified as core genes in the network and potential therapeutic targets of DPC. Discussion: The current study provides new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.

show abstract

Targeting of oncogenic signaling pathways by berberine for treatment of colorectal cancer

Cited by 26 publications

References 110 publications

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Mechanisms of Core Chinese Herbs against Colorectal Cancer: A Study Based on Data Mining and Network Pharmacology

Identification of critical pathways and potential therapeutic targets in Poorly differentiated duodenal papilla adenocarcinoma

Contact Info

Product

Resources

About