Role of Curculigo Orchioides in the Proliferation and Apoptosis of Breast Cancer Michigan Cancer Foundation-7 (MCF-7) Cells Under Network Pharmacology

2022 ◽  
Vol 12 (1) ◽  
pp. 121-128
Author(s):  
Xiaoyong Zhou ◽  
An Qian ◽  
Panfei Hou
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Network Pharmacology ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
High Dose ◽  
Promoting Effect ◽  
Blank Control Group ◽  
Curculigo Orchioides ◽  
Proliferation And Apoptosis

Based on network pharmacology (NP), the effects of curculigo orchioides (CO) granules alone or CO granules along with tamoxifen on the proliferation and apoptosis (P&A) of human breast cancer (BC) cells were explored. A search database was constructed to obtain the active components (ACs) of CO and related target genes to perform disease mapping, and a BC target map was constructed to perform related pathway enrichment analysis (PEA). The blank control group (CG), estrogen group (EG), and tamoxifen group (TG) were set as controls to observe the effects of CO granules alone and CO granules along with tamoxifen. The PEA showed that the effect of CO on BC may be related to the cooperation of its ACs. The target of action may be related to cell cycle and proliferation, growth factors, metabolic pathways, etc. Different concentrations of CO had different effects, CO granules of various concentrations had no obvious growth-promoting effect (P < 0.05), and so did CO combined with tamoxifen (P > 0.05); high-dose (H-D) CO combined with tamoxifen can induce cell apoptosis (P < 0.05). Through NP, the ACs of CO and related targets of BC were predicted and analyzed. At the same time, it was proved that CO granules are safe in clinical use, and the combined effect of tamoxifen is better in the treatment of estrogen-positive patients, providing reference for the follow-up use of CO in the treatment of BC.

scholarly journals Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaobo Zhang ◽  
Tao Shen ◽  
Xin Zhou ◽  
Xuehua Tang ◽  
Rui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Perennial Herb ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Prunella Vulgaris ◽  
Biological Mechanisms ◽  
Active Constituents

Abstract Prunella vulgaris L, a perennial herb widely used in Asia in the treatment of various diseases including cancer. In vitro studies have demonstrated the therapeutic effect of Prunella vulgaris L. against breast cancer through multiple pathways. However, the nature of the biological mechanisms remains unclear. In this study, a Network pharmacology based approach was used to explore active constituents and potential molecular mechanisms of Prunella vulgaris L. for the treatment of breast cancer. The methods adopted included active constituents prescreening, target prediction, GO and KEGG pathway enrichment analysis. Molecular docking experiments were used to further validate network pharmacology results. The predicted results showed that there were 19 active ingredients in Prunella vulgaris L. and 31 potential gene targets including AKT1, EGFR, MYC, and VEGFA. Further, analysis of the potential biological mechanisms of Prunella vulgaris L. against breast cancer was performed by investigating the relationship between the active constituents, target genes and pathways. Network analysis showed that Prunella vulgaris L. exerted a promising preventive effect on breast cancer by acting on tumor-associated signaling pathways. This provides a basis to understand the mechanism of the anti-breast cancer activity of Prunella vulgaris L.

scholarly journals Study on the mechanism of Erzhi Pill in the treatment of breast cancer based on network pharmacology

2021 ◽  
Vol 245 ◽  
pp. 03055
Author(s):  
Fahu Yuan ◽  
Xinghua Liao ◽  
Tongcun Zhang
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Suppressor Gene ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Components ◽  
Annotation Database ◽  
Amino Terminal ◽  
Target Network

Objective: To explore the possible mechanism of Erzhi Pill in the treatment of breast cancer based on network pharmacology. Methods: Through systematic pharmacology database and analysis platform of Traditional Chinese medicine (TCMSP) and literature review, the candidate active ingredients and corresponding targets of Erzhi Pill were retrieved and collected. The UniProt database and the Human Genome Annotation Database (Genecards) were used to compare the results, and the potential target genes were obtained for the coincidence of Erzhi Pill and breast cancer. Cytoscape was used to construct the “candidate component - action target” network of Erzhi Pill. Generate Style from Statistics tool in String database and Cytoscape software was combined to construct protein interaction network.The Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis and GO classification enrichment analysis for targets of Erzhi Pill were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID ) bioinformation resource Database. Results: A total of 21 candidate active components, including Beta-sitosterol, Quercetin, Luteolin, Demethylwedelolactone, Kaempferol and so on, were screened from Erzhi Pill, corresponding to 158 target genes, including vascular endothelial growth factor (VEGF), amino-terminal kinase (C-Jun), proto-oncogene (C-MYC), matrix metalloproteinase-9 (MMP-9), and mainly involved in TNF-α, phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt), tumor suppressor gene p53, toll-like receptor family and other signaling pathways. Conclusion: This study predicted the possible mechanism of action of Erzhi Pill in the treatment of breast cancer based on the method of network pharmacology, and provided a direction for further research.

Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

2020 ◽  
Vol 20 ◽  
Author(s):  
Weihong Qu ◽  
Jianguo Zhao ◽  
Yaqing Wu ◽  
Ruian Xu ◽  
Shaowu Liu
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Control Group ◽  
High Dose ◽  
Blank Control Group ◽  
Adeno Associated Virus ◽  
Tumor Tissues ◽  
Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

scholarly journals Effects of Hexachlorocyclohexane (HCH-γ-Isomer, Lindane) Intoxication on the Proliferation and Apoptosis in Rat Testes

2009 ◽  
Vol 78 (4) ◽  
pp. 615-620 ◽  
Author(s):  
Hayati Yuksel ◽  
Erkan Karadas ◽  
Hikmet Keles ◽  
Hasan Huseyin Demirel
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Histopathological Changes ◽  
Proliferation And Apoptosis ◽  
Group A ◽  
Higher Doses ◽  
Group 1

In this study, experimentally lindane-induced histopathological changes and proliferation and/or apoptosis in germ cells in the rat testes were investigated. A total of 40 healthy fertile 3-month-old male rats were used. Animals were divided into 4 groups, each containing 10 rats. Group 1 (control) was given only pure olive oil, Groups 2, 3 and 4 were administered lindane at 10, 20 and 40 mg/kg/bw, respectively, by gastric gavage for 30 days. Microscopically, degenerative changes were observed in the lindane-treated groups. For proliferative activity PCNA immunolabelling and for germ cells apoptosis TUNEL methods were performed. Although a strong PCNA positivity in the control group was observed, a gradual decrease was noted in the lindane-treated groups especially at higher doses. Significant increases of apoptosis were seen in the lindane-treated groups compared to the control group. A decrease in testosterone concentrations was observed in lindane-treated groups compared to the control group. The study indicates that high-dose lindane intoxication contributes to the suppression of spermatogenesis through a reduction of germ cell proliferation and an increase of germ cell death in rat testes.

scholarly journals Network Pharmacology and Molecular Docking Suggest the Mechanism for Biological Activity of Rosmarinic Acid

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Minglong Guan ◽  
Lan Guo ◽  
Hengli Ma ◽  
Huimei Wu ◽  
Xiaoyun Fan
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Rosmarinic Acid ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis

Rosmarinic acid (RosA) is a natural phenolic acid compound, which is mainly extracted from Labiatae and Arnebia. At present, there is no systematic analysis of its mechanism. Therefore, we used the method of network pharmacology to analyze the mechanism of RosA. In our study, PubChem database was used to search for the chemical formula and the Chemical Abstracts Service (CAS) number of RosA. Then, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to evaluate the pharmacodynamics of RosA, and the Comparative Toxicogenomics Database (CTD) was used to identify the potential target genes of RosA. In addition, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes were carried out by using the web-based gene set analysis toolkit (WebGestalt). At the same time, we uploaded the targets to the STRING database to obtain the protein interaction network. Then, we carried out a molecular docking about targets and RosA. Finally, we used Cytoscape to establish a visual protein-protein interaction network and drug-target-pathway network and analyze these networks. Our data showed that RosA has good biological activity and drug utilization. There are 55 target genes that have been identified. Then, the bioinformatics analysis and network analysis found that these target genes are closely related to inflammatory response, tumor occurrence and development, and other biological processes. These results demonstrated that RosA can act on a variety of proteins and pathways to form a systematic pharmacological network, which has good value in drug development and utilization.

scholarly journals TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer

2019 ◽  
Vol 111 (11) ◽  
pp. 1202-1215 ◽  
Author(s):  
Utpal K Mukhopadhyay ◽  
Chetan C Oturkar ◽  
Christina Adams ◽  
Nadi Wickramasekera ◽  
Sanjay Bansal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Target Genes ◽  
Molecular Taxonomy ◽  
Estrogen Receptor Beta ◽  
Control Group ◽  
Wild Type ◽  
International Consortium ◽  
Tp53 Status ◽  
Receptor Beta

Abstract Background Anti-tumorigenic vs pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative breast cancer (TNBC). Methods ESR2-TP53 interaction was analyzed with multiple assays including the in situ proximity ligation assay. Transcriptional effects on TP53-target genes and cell proliferation in response to knocking down or overexpressing ESR2 were determined. Patient survival according to ESR2 expression levels and TP53 mutation status was analyzed in the basal-like TNBC subgroup in the Molecular Taxonomy of Breast Cancer International Consortium (n = 308) and Roswell Park Comprehensive Cancer Center (n = 46) patient cohorts by univariate Cox regression and log-rank test. All statistical tests are two-sided. Results ESR2 interaction with wild-type and mutant TP53 caused pro-proliferative and anti-proliferative effects, respectively. Depleting ESR2 in cells expressing wild-type TP53 resulted in increased expression of TP53-target genes CDKN1A (control group mean [SD] = 1 [0.13] vs ESR2 depletion group mean [SD] = 2.08 [0.24], P = .003) and BBC3 (control group mean [SD] = 1 [0.06] vs ESR2 depleted group mean [SD] = 1.92 [0.25], P = .003); however, expression of CDKN1A (control group mean [SD] = 1 [0.21] vs ESR2 depleted group mean [SD] = 0.56 [0.12], P = .02) and BBC3 (control group mean [SD] = 1 [0.03] vs ESR2 depleted group mean [SD] = 0.55 [0.09], P = .008) was decreased in cells expressing mutant TP53. Overexpressing ESR2 had opposite effects. Tamoxifen increased ESR2-mutant TP53 interaction, leading to reactivation of TP73 and apoptosis. High levels of ESR2 expression in mutant TP53-expressing basal-like tumors is associated with better prognosis (Molecular Taxonomy of Breast Cancer International Consortium cohort: log-rank P = .001; hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.84, univariate Cox P = .02). Conclusions TP53 status is a determinant of the functional duality of ESR2. Our study suggests that ESR2-mutant TP53 combination prognosticates survival in TNBC revealing a novel strategy to stratify TNBC for therapeutic intervention potentially by repurposing tamoxifen.

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

1997 ◽  
Vol 15 (6) ◽  
pp. 2312-2321 ◽  
Author(s):  
A M Gianni ◽  
S Siena ◽  
M Bregni ◽  
M Di Nicola ◽  
S Orefice ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Dose ◽  
Treated Group ◽  
Multicenter Trial ◽  
Control Group ◽  
High Dose ◽  
Axillary Nodes ◽  
Major Toxicity ◽  
Nonhematologic Toxicity

PURPOSE To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

scholarly journals Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Mengshi Tang ◽  
Xi Xie ◽  
Pengji Yi ◽  
Jin Kang ◽  
Jiafen Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Binding Activity ◽  
New Combination ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Potential Mechanism

Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

scholarly journals Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

2019 ◽  
Vol 74 (2) ◽  
pp. 353-370 ◽  
Author(s):  
Li Tian ◽  
Weibin Qian ◽  
Qiuhai Qian ◽  
Wei Zhang ◽  
Xinrui Cai
Keyword(s):  
Low Dose ◽  
Area Postrema ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Delayed Emesis ◽  
Blank Control Group ◽  
Qrt Pcr ◽  
Underlying Mechanisms ◽  
Different Doses

Abstract Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

scholarly journals Construction of a Potential Breast Cancer-Related miRNA-mRNA Regulatory Network

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Xinhong Liu ◽  
Feng Chen ◽  
Fang Tan ◽  
Fang Li ◽  
Ruokun Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Target Genes ◽  
Differential Expression Analysis ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Epithelial Tissue ◽  
Hub Genes ◽  
Geo Database

Background. Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland and has become the most common malignancy in women. The regulation of the expression of related genes by microRNA (miRNA) plays an important role in breast cancer. We constructed a comprehensive breast cancer-miRNA-gene interaction map. Methods. Three miRNA microarray datasets (GSE26659, GSE45666, and GSE58210) were obtained from the GEO database. Then, the R software “LIMMA” package was used to identify differential expression analysis. Potential transcription factors and target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted. The BRCA GE-mRNA datasets (GSE109169 and GSE139038) were downloaded from the GEO database for identifying differentially expressed genes (DE-genes). Next, GO annotation and KEGG pathway enrichment analysis were conducted. A PPI network was then established, and hub genes were identified via Cytoscape software. The expression and prognostic roles of hub genes were further evaluated. Results. We found 6 upregulated differentially expressed- (DE-) miRNAs and 18 downregulated DE-miRNAs by analyzing 3 Gene Expression Omnibus databases, and we predicted the upstream transcription factors and downstream target genes for these DE-miRNAs. Then, we used the GEO database to perform differential analysis on breast cancer mRNA and obtained differentially expressed mRNA. We found 10 hub genes of upregulated DE-miRNAs and 10 hub genes of downregulated DE-miRNAs through interaction analysis. Conclusions. In this study, we have performed an integrated bioinformatics analysis to construct a more comprehensive BRCA-miRNA-gene network and provide new targets and research directions for the treatment and prognosis of BRCA.

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