Dataset Information

Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.

ABSTRACT: Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer. In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI both in vitro and in vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities. Overall, our study provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies.

SUBMITTER: Wang N

PROVIDER: S-EPMC5674025 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.

Wang Neng N Zheng Yifeng Y Gu Jiangyong J Cai Youli Y Wang Shengqi S Zhang Fengxue F Chen Jianping J Situ Honglin H Lin Yi Y Wang Zhiyu Z

Scientific reports 20171106 1

Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer. In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulati ...[more]

PMID: 29109519

Similar Datasets

Project description:Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality, but the therapies remain limited. Bupi Yishen Formula (BYF) - a patent traditional Chinese medicine (TCM) formula - has been proved to be effective for CKD treatment in a high-quality clinical trial. However, BYF's underlying mechanism is unclear. Thus, we aimed to reveal BYF pharmacological mechanism against CKD by network pharmacology and experimental studies. Network pharmacology-based analysis of the drug-compound-target interaction was used to predict the potential pharmacological mechanism and biological basis of BYF. We performed a comprehensive study by detecting the expression levels of fibrotic and inflammatory markers and main molecules of candidate signal pathway in adenine-induced CKD rats and TGF-β1-induced HK-2 cells with the treatment of BYF by western blotting and RT-qPCR analyses. Using small interfering RNA, we assessed the effect of BYF on the TLR4-mediated NF-κB mechanism for CKD renal fibrosis and inflammation. Network pharmacology analysis results identified 369 common targets from BYF and CKD. Based on these common targets, the BYF intervention pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We found that Toll-like receptor (TLR) and NF-κB signaling pathways were enriched. Then, we demonstrated that BYF significantly improved the adenine-induced CKD rat model condition by kidney dysfunction improvement and reversing renal fibrosis and inflammation. Subsequently, we investigated BYF's effect on the TLR4/NF-κB signaling pathway. We found that TLR4 and phospho-NF-κB (p-p65 and p-IKβα) expression was significantly upregulated in adenine-induced CKD rats, then partially downregulated by BYF. Furthermore, BYF inhibited fibrotic and inflammatory responses, as well as TLR4, p-p65, and p-IKβα in TGF-β1-induced HK-2 cells. Additionally, the BYF inhibitory effect on fibrosis and inflammation, and NF-κB pathway activation were significantly reduced in TGF-β1-induced HK-2 cells transfected with TLR4 siRNA. Altogether, these findings demonstrated that the suppression of TLR4-mediated NF-κB signaling was an important anti-fibrotic and anti-inflammatory mechanism for BYF against CKD. It also provided a molecular basis for new CKD treatment drug candidates.

Project description:Le-Cao-Shi (LCS) has long been used as a folk traditional Chinese medicine formula against liver injuries, whereas its pharmacological mechanisms remain elusive. Our study aims to investigate the underlying mechanism of LCS in treating liver injuries via integrated network pharmacology, metabonomics, and experimental validation. By network pharmacology, 57 compounds were screened as candidate compounds based on ADME parameters from the LCS compound bank (213 compounds collected from the literature of three single herbs). According to online compound-target databases, the aforementioned candidate compounds were predicted to target 87 potential targets related to liver injuries. More than 15 pathways connected with these potential targets were considered vital pathways in collectively modulating liver injuries, which were found to be relevant to cancer, xenobiotic metabolism by cytochrome P450 enzymes, bile secretion, inflammation, and antioxidation. Metabonomics analysis by using the supernatant of the rat liver homogenate with UPLC-Q-TOF/MS demonstrated that 18 potential biomarkers could be regulated by LCS, which was closely related to linoleic acid metabolism, glutathione metabolism, cysteine and methionine metabolism, and glycerophospholipid metabolism pathways. Linoleic acid metabolism and glutathione metabolism pathways were two key common pathways in both network pharmacology and metabonomics analysis. In ELISA experiments with the CCl4-induced rat liver injury model, LCS was found to significantly reduce the levels of inflammatory parameters, decrease liver malondialdehyde (MDA) levels, and enhance the activities of hepatic antioxidant enzymes, which validated that LCS could inhibit liver injuries through anti-inflammatory property and by suppressing lipid peroxidation and improving the antioxidant defense system. Our work could provide new insights into the underlying pharmacological mechanisms of LCS against liver injuries, which is beneficial for its further investigation and modernization.

Project description:BackgroundThe Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear.MethodsThe main components of GQWTF were detected by LC-MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein-protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments.ResultsFirst, the "herb-channel tropism" network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, "compound-target" network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a "formula-compound-pathway-symptom" network was constructed to represent a global view of GQWTF in the treatment of T2DM.ConclusionsThis study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

Project description:Objectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms). Methods: The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein-protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula's CHD modules). The molecular characteristics of LXNX formula's CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms). Results: We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups. Conclusion: G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula's pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that Pinellia ternata (Banxia) has relatively strong adjustive functions on the two key targets.

Dataset Information

Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.

Publications

Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets