scholarly journals Network pharmacology and RNA sequencing studies on triterpenoid saponins from Bupleurum chinense for the treatment of breast cancer

RSC Advances ◽  
2019 ◽  
Vol 9 (70) ◽  
pp. 41088-41098
Author(s):  
Danqi Li ◽  
Da Liu ◽  
Dandan Yue ◽  
Pinyi Gao ◽  
Cheng Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Sequencing ◽  
Therapeutic Targets ◽  
Network Pharmacology ◽  
Biological Mechanisms ◽  
Triterpenoid Saponins ◽  
Sequencing Studies

The network pharmacology and RNA sequencing studies were used to explore potential therapeutic targets and biological mechanisms of B. chinense for the treatment of breast cancer.

scholarly journals Retinoic Acid Sensitivity of Triple-Negative Breast-Cancer Cells Characterized by Constitutive Activation of the NOTCH1 Pathway: The Role of RARβ

2020 ◽  
Author(s):  
Gabriela Paroni ◽  
Adriana Zanetti ◽  
Maria Monica Barzago ◽  
Mami Kurosaki ◽  
Luca Guarrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retinoic Acid ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Proliferative Activity ◽  
Triple Negative ◽  
Proliferation Index ◽  
Constitutive Activation ◽  
Sequencing Studies

Abstract Background: All-trans retinoic-acid (ATRA) is a promising agent in the personalized treatment/chemo-prevention of breast-cancer. Triple-negative breast-cancer (TNBC) accounts for 15-20% of all mammary tumours and share common features such as a high proliferation index and a basal-like gene expression signature. In spite of this, TNBC is very heterogeneous and lacks effective therapeutic strategies.Methods: We profile eighteen TNBC breast-cancer cell-lines for their sensitivity to the anti-proliferative action of ATRA. In addition, we perform RNA-sequencing studies in two of the most sensitive cell-lines exposed to ATRA, a γ-secretase inhibitor and combinations thereof. Results: The only three TNBC cell-lines (HCC-1599, MB-157 and MDA-MB-157) endowed with ATRA-sensitivity are characterized by constitutive activation of the NOTCH1 γ-secretase product, N1ICD and we identify the associated genetic aberrations of the NOTCH1-gene. N1ICD expression renders HCC-1599, MB-157 and MDA-MB-157 cells sensitive not only to ATRA, but also to γ-secretase inhibitors, like DAPT [N-(N-(3,5-difluorophenacetyl)-L-alanyl)-S-phenylglycine-t-butyl-ester] and PF-03084014. The anti-proliferative action of ATRA and γ-secretase inhibitors is complementary, as combinations of ATRA and DAPT or PF-03084014 cause synergistic effects. This synergism is confirmed in mouse xenografts of HCC-1599 cells. RNA-sequencing studies performed in HCC-1599 and MB-157 cells exposed to ATRA and DAPT demonstrate that the two compounds act on common gene-sets, some of which belong to the NOTCH1 pathway. ATRA inhibits the growth of HCC-1599, MB-157 and MDA-MB-157 cells via RARα, which up-regulates several retinoid target-genes, including RARβ. RARβ induction is observed only in HCC-1599, MB-157 and MDA-MB-157 cells, as the other TNBC cell-lines lack ATRA-dependent stimulation of the retinoid-receptor. RARβ is a key determinant of ATRA anti-proliferative activity, as its silencing suppresses the effects exerted by the retinoid. Conclusions: We demonstrate that ATRA exerts a significant anti-tumor action in TNBC cells characterized by constitutive NOTCH1 activation. We show that ATRA enhances the anti-tumor activity of γ-secretase inhibitors in an additive/synergistic manner. We support the idea that ATRA anti-proliferative activity is mediated by the Retinoid-Acid-Receptor-β (RARβ). The present study represents the basis for the design of clinical trials on the efficacy of combinations between ATRA and γ-secretase inhibitors in the treatment of patients affected by a specific subtype of TNBC.

scholarly journals A Network Pharmacology Study on the Molecular Mechanisms of FDY003 for Breast Cancer Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ho-Sung Lee ◽  
In-Hee Lee ◽  
Kyungrae Kang ◽  
Sang-In Park ◽  
Seung-Joon Moon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Anticancer Efficacy ◽  
Artemisia Capillaris

Herbal medicines have drawn considerable attention with regard to their potential applications in breast cancer (BC) treatment, a frequently diagnosed malignant disease, considering their anticancer efficacy with relatively less adverse effects. However, their mechanisms of systemic action have not been understood comprehensively. Based on network pharmacology approaches, we attempted to unveil the mechanisms of FDY003, an herbal drug comprised of Lonicera japonica Thunberg, Artemisia capillaris Thunberg, and Cordyceps militaris, against BC at a systemic level. We found that FDY003 exhibited pharmacological effects on human BC cells. Subsequently, detailed data regarding the biochemical components contained in FDY003 were obtained from comprehensive herbal medicine-related databases, including TCMSP and CancerHSP. By evaluating their pharmacokinetic properties, 18 chemical compounds in FDY003 were shown to be potentially active constituents interacting with 140 BC-associated therapeutic targets to produce the pharmacological activity. Gene ontology enrichment analysis using g:Profiler indicated that the FDY003 targets were involved in the modulation of cellular processes, involving the cell proliferation, cell cycle process, and cell apoptosis. Based on a KEGG pathway enrichment analysis, we further revealed that a variety of oncogenic pathways that play key roles in the pathology of BC were significantly enriched with the therapeutic targets of FDY003; these included PI3K-Akt, MAPK, focal adhesion, FoxO, TNF, and estrogen signaling pathways. Here, we present a network-perspective of the molecular mechanisms via which herbal drugs treat BC.

scholarly journals Exploring the Modulatory Mechanism of Eleng Capsule in the Treatment of Endometriosis Based on Integrated Strategy of Transcriptomics Combined With Network Pharmacology

2020 ◽  
Author(s):  
Weilin Zheng ◽  
Jie Wang ◽  
Jiangyong Gu ◽  
Jiayi Wu ◽  
Tao Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Targets ◽  
Gene Set Enrichment Analysis ◽  
Mass Spectrometry Analysis ◽  
Network Pharmacology ◽  
Mesenchymal Transition ◽  
Tof Ms

Abstract BackgroundEndometriosis causes severe chronic pelvic pain and infertility. Chinese medicine plays an active role in the treatment of endometriosis. ELeng Capsule(ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. The previous studies have shown that ELC inhibits endometriosis. However, the mechanisms of action of ELC have not been characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC.Methods Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis(UPLC-Q-TOF/MS) was used to identify the compounds in ELC.And network pharmacology was used to analyze the network of targets and identified compounds of ELC. Apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) assay.The protein expression of VEGFA,VEGFB,VEGFC and α-SMA in the ectopic endometrium were identified by immunohistochemistry(IHC).The level of VEGFA,VEGFB and IL1-β in serum were used by ELISA. Further, RNA-sequencing was used to identify differentially expressed genes (DEGs) in ELC. Biological functions and pathways were determined through the Gene Ontology(GO) and Kyoto encyclopedia of genes and genomes pathway(KEGG) analyses. In addition, Gene Set Enrichment Analysis (GSEA) analysis was used to further analyze the genetic network and modular genetics. ResultsWe had identified 26 new bioactive compounds in ELeng Capsule by UPLC-Q-TOF/MS analysis. The KEGG pathways of ELC associtaed targets related to neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the vascular endothelial growth factor signaling pathway by network pharmacology analysis.Further, ELC could induce cell apoptosis, inhibit angiogenesis through reduce the expression of VEGFA and VEGFC, and inhibit the fibrosis through reduce the expression of α-SMA in ectopic lesions(P＜0.05). In addition, the development of endometriosis in the rat model may be related to mechanisms of inflammation,epithelial-mesenchymal transition(EMT) by RNA-sequencing. And the targets in the treatment of ELC were predominantly associated with actin and cytoskeleton,EMT,focal adhesion,and inflammatory immunity based on the DEGs analysis. In additon, the GSEA analysis showed that the treatment of ELC was associated with the Notch signaling pathway, Hippo signaling pathway, etc.ConclusionELeng Capsules exerted beneficial effects against endometriosis, potentially by induce apoptosis,modulating the angiogenesis,cytoskeleton, epithelial-mesenchymal transition(EMT), and cell junction-associated pathways,etc. These findings could provide evidence for an innovative treatment strategy and novel therapeutic targets for endometriosis.

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 Network pharmacology reveals hub bio-active ingredients and possible mechanisms of a Chinese herbal prescription Ru-kang-yin against breast cancer

2020 ◽  
Author(s):  
Shirun Chu ◽  
Fang Chen ◽  
Jun Li ◽  
Mei Yang ◽  
Delin Xu
Keyword(s):  
Breast Cancer ◽  
Therapeutic Targets ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Active Components ◽  
Active Compounds ◽  
Chinese Herbal ◽  
Underlying Mechanisms ◽  
Herbal Prescription

Abstract Background Ru-kang-yin (RKY), a traditional Chinese herbal prescription, has been clinically used as adjuvant therapy for breast cancer via inhibiting cell invasion, proliferation, and promoting apoptosis. However, its anti-breast cancer bio-active ingredients and possible mechanisms are still unclear. In the present study, the hub bio-active compounds and underlying mechanisms of RKY in treatment of breast cancer were systematically elucidated by the approach of network pharmacology. Methods By using network pharmacology approach, a total of 53 nonredundant bio-active components met the drug screening criteria and 155 putative targets of RKY in treatment of breast cancer were identified. Besides, 381 potential breast cancer-related targets were obtained. Among of the targets, 56 shared targets of RKY and breast cancer were acquired. Results Based on topological network analysis of PPI network of shared targets, 19 hub therapeutic targets of RKY against breast cancer were obtained. GO and KEGG pathway enrichment analysis of core therapeutic targets showed that the core targets remarkably involved in multiple biological functions and KEGG pathways which mainly participated in inflammatory response, cell proliferation, and apoptosis. Conclusions These findings uncover the hub bio-active compounds and underlying mechanisms of RKY against breast cancer and provide crucial information regarding using RKY as a promising candidate for treating breast cancer.

Exosomal circular RNAs derived from serum: Promising biomarkers for therapeutic targets and prognosis of triple-negative breast cancer (TNBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3528-3528
Author(s):  
Sujin Yang ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
Rna Sequencing ◽  
Therapeutic Targets ◽  
Bioinformatic Analysis ◽  
Circular Rnas ◽  
Invasion And Metastasis ◽  
Tnbc Cell ◽  
Tumor Tissues ◽  
Serum Exosomes ◽  
Proliferation And Invasion

3528 Background: Exosomes are well known by the "exosomal shuttle" that delivers oncogenic microRNAs (miRNAs), mRNAs, circular RNAs (circRNAs) and proteins to the recipient cells and tumor microenvironment, and may be used as promising biomarkers for disease diagnosis. This study aims to provide a theoretical basis to use stable exosomal circRNAs as new biomarkers for predicting the development, metastasis and therapeutic targets of TNBC. Methods: A strategy combining RNA-sequencing technique, bioinformatic analysis and RT-qPCR was used to determine the level of differential expressed circRNAs in serum exosomes samples (n = 43) from TNBC patients compared with non-TNBC patients. The expression of circHSDL2 were also detected in tumor tissues (n = 20) from TNBC patients and breast cancer cell lines by qRT-PCR. Cell cycle analysis, the wound healing assays and transwell assays were used to investigate the function of circHSDL2 in proliferation, invasion and metastasis of TNBC cells. FISH, dual-luciferase reporter and functional assays were performed to confirm the interaction between circHSDL2 and let-7a-2-3p in TNBC cells. Results: We profiled the circRNAs in the serum exosomes samples from TNBC patients and non-TNBC patients by RNA sequencing and detected 803 significantly differentially-expressed circRNAs. After bioinformatic analysis, circHSDL2 was chose to further study. RT-qPCR results showed that higher expression of circHSDL2 in TNBC cell lines and tumor tissues from TNBC patients. Moreover, overexpression of circHSDL2 promoted TNBC cells proliferation and invasion, while knockdown of circHSDL2 inhibited TNBC cells proliferation and invasion. Mechanistically, circHSDL2 acted as a "miRNAs sponge" to absorb let-7a-2-3p; let-7a-2-3p inhibited TNBC cell invasion and metastasis. Kaplan-Meier plots showed lower expression of let-7a-2-3p was connected to poor prognosis in TNBC metastasis patients from TCGA database. Conclusions: The expression of circHSDL2 was found significantly upregulated in serum exosomes and tumor tissues from TNBC patients. Moreover, circHSDL2 could promote cell proliferation, invasion and metastasis in TNBC cells. CircHSDL2 might be function as competing endogenous RNAs (ceRNAs) by targeting let-7a-2-3p in the progression of TNBC. Therefore, this study provides a fresh perspective on novel therapeutic targets and potential biomarkers for TNBC from exosomal circRNAs.

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