Network pharmacology-based analysis for unraveling potential cancer-related molecular targets of Egyptian propolis phytoconstituents accompanied with molecular docking and in vitro studies

Multi-level mechanism of action of propolis constituents in cancer treatment using an integrated approach of network pharmacology-based analysis, molecular docking and in vitro cytotoxicity testing.

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Exploring the effect of Polyphyllin I on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210816141436 ◽

2021 ◽

Vol 24 ◽

Author(s):

Shuxian Yu ◽

Wenhui Gao ◽

Puhua Zeng ◽

Chenglong Chen ◽

Zhuo Liu ◽

...

Keyword(s):

Molecular Docking ◽

Liver Cancer ◽

Mechanism Of Action ◽

Active Ingredient ◽

Vehicle Group ◽

Network Pharmacology ◽

Dependent Manner ◽

In Vitro Experiments ◽

Concentration Dependent Manner

Aim and Objective: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. Materials and Methods: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. Results: Bioinformatics analysis found that PPI had totally 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). Conclusion: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

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Bellidifolin Inhibits Proliferation of A549 Cells by Regulating STAT3/COX-2 Expression and Protein Activity

Journal of Oncology ◽

10.1155/2020/1723791 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Li Yan ◽

Luo Yali ◽

Li Chenghao ◽

Feng Caiqin ◽

Zhu Zhongbo ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Docking ◽

Cancer Treatment ◽

Cancer Cells ◽

A549 Cells ◽

Lung Cancer Cells ◽

Network Pharmacology ◽

Cox 2 ◽

A549 Lung

Objectives. Bellidifolin (BEL) is one type of tetraoxygenated xanthone that is particularly found in Swertia and Gentiana (Gentianaceae). Despite its broad range of pharmacological activities, it is still unclear whether BEL could be used for lung cancer treatment. Hence, we presently demonstrate the roles of BEL towards the proliferative inhibition of the prototypical A549 lung cancer cells. Materials and Methods. The antiproliferative activity of BEL was initially verified by cellular experiments. A network pharmacology method was then pursued to assess BEL potential molecular targets from the platform for pharmacological analysis of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease enrichment of potential targets and construction of compound-target-disease network maps were performed based on a total of 20 diseases. Two core targets related to the BEL-mediated effect in A549 cells were obtained by importing potential targets into a protein-protein interaction database (STRING) and also analyzing respective data of related targets into this database. Last, these core targets were examined by in vitro analysis and molecular docking. Results. CCK8 assays indicated that treatment with 50–100 μm BEL had an inhibitory effect on the proliferation of human A549 lung cancer cells, whereas this effect was time- and concentration-dependent. As control, treatment with 50–100 μm BEL did not inhibit the proliferation of normal lung epithelial cells (BEAS-2b cell line). H&E staining of BEL-treated A549 cells showed that, upon an increase of drug concentration, nuclear condensation and fragmentation were largely observed. Cell cycle analysis showed that in vitro treatment with 75–100 μm BEL could block A549 cells in S and G2 phases. Western blot analyses showed that after 72 hours of BEL treatment, the level of caspase-8/3 in A549 cells increased, and the level of PARP1 decreased in a dose-dependent manner. Network pharmacology analysis also indicated that lung cancer was the major disease susceptible to BEL treatment. At the same time, STAT3 and COX-2 were identified as two core targets of BEL in lung cancer treatment. Functional analyses further revealed that the cytotoxicity effect of BEL in A549 cells potentially involved the STAT3/COX-2 pathway. Moreover, molecular docking analysis indicated that BEL structure properly matches with COX-2 and STAT3 in space shape, thus illustrating the putative molecular mechanism of BEL’s anticancer effect. Conclusions. Based on a series of in vitro analyses, network pharmacology, and molecular docking, the potential mechanism involving the antiproliferative and cytotoxic effects of BEL in lung cancer cells was investigated. Our study may help providing some theoretical basis for the discovery of novel phytotherapy drugs applicable for the treatment of lung cancer.

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Systematic Elucidation of the Mechanism of Action of Curcumin Against Colorectal Cancer via Network Pharmacology Approach

10.21203/rs.3.rs-535607/v1 ◽

2021 ◽

Author(s):

Xinyue Han ◽

Yimin Xu ◽

Xiaoqiang Liu ◽

Yuan Li ◽

Cui Guo ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Mechanism Of Action ◽

Experimental Verification ◽

Enrichment Analysis ◽

Network Pharmacology ◽

In Vitro Experiments

Abstract Background: Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated.Aim: To investigate the mechanism of action of curcumin in the treatment of CRC via network pharmacology, molecular docking and experimental verification.Methods: The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking and in vitro experiments.Results: A total of 30 potential targets of curcumin for CRC treatment were collectedThe core targets included AKT1, EGFR and STAT3 were identified. GO function enrichment analysis showed 140 items, and KEGG pathway enrichment analysis showed 61 signaling pathways, that were related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway and PI3K-Akt signali-ng pathway. In vitro experimental verification showed that curcumin could promote the apoptosis of CRC cells, and the key proteins of these signaling pathways were differentially expressed.Conclusion: This study explored the targets and pathways of curcumin in the treatment of colorectal cancer. In vitro experiments showed that curcumin has a therapeutic effect against CRC by inhibiting PI3K-Akt signaling pathway. Our results will lay a foundation for subsequent clinical research and drug development.

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Inhibition of Pituitary Gonadotropin Secretion by the Gonadotropin-Releasing Hormone Antagonist Antide. I. In Vitro Studies on Mechanism of Action*

Endocrinology ◽

10.1210/endo-128-4-2036 ◽

1991 ◽

Vol 128 (4) ◽

pp. 2036-2040 ◽

Cited By ~ 3

Author(s):

DOUGLAS R. DANFORTH ◽

ROBERT F. WILLIAMS ◽

KEITH GORDON ◽

GARY D. HODGEN

Keyword(s):

Mechanism Of Action ◽

Gonadotropin Releasing Hormone ◽

In Vitro Studies ◽

Gonadotropin Secretion ◽

Releasing Hormone ◽

Pituitary Gonadotropin

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In vitro studies on the interaction between human serum albumin and fosfomycin disodium salt, an antibiotic drug by multi-spectroscopic and molecular docking methods

Molecular Biology Reports ◽

10.1007/s11033-014-3092-y ◽

2014 ◽

Vol 41 (4) ◽

pp. 2377-2387 ◽

Cited By ~ 4

Author(s):

Manjunath D. Meti ◽

Kirthi S. Byadagi ◽

Sharanappa T. Nandibewoor ◽

Shrinivas D. Joshi ◽

Uttam A. More ◽

...

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Disodium Salt ◽

In Vitro Studies ◽

Antibiotic Drug

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Interactions between phenolic constituents of Scutellaria salviifolia and key targets associated with inflammation: network pharmacology, molecular docking analysis and in vitro assays

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2021.2019119 ◽

2021 ◽

pp. 1-14

Author(s):

Zeynep Dogan ◽

Vahap Murat Kutluay ◽

Yasin Genc ◽

Iclal Saracoglu

Keyword(s):

Molecular Docking ◽

In Vitro Assays ◽

Network Pharmacology ◽

Docking Analysis ◽

Phenolic Constituents ◽

Molecular Docking Analysis

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Prediction of potential cancer-related molecular targets of North African plants constituents using network pharmacology-based analysis

Journal of Ethnopharmacology ◽

10.1016/j.jep.2019.111826 ◽

2019 ◽

Vol 238 ◽

pp. 111826 ◽

Cited By ~ 15

Author(s):

Eman Shawky

Keyword(s):

Molecular Targets ◽

Network Pharmacology ◽

North African ◽

African Plants ◽

Potential Cancer

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Molecular docking simulation and in vitro studies on estrogenic activities of flavonoids from leaves of Carya cathayensis Sarg

Steroids ◽

10.1016/j.steroids.2020.108726 ◽

2020 ◽

Vol 163 ◽

pp. 108726

Author(s):

Jing-Jing Lu ◽

Fang-Mei Zhou ◽

Xu-Jiao Hu ◽

Jing-Jing Fang ◽

Cai-Xia Liu ◽

...

Keyword(s):

Molecular Docking ◽

Docking Simulation ◽

In Vitro Studies ◽

Molecular Docking Simulation ◽

Carya Cathayensis ◽

Carya Cathayensis Sarg

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Mechanism of Action of Bu-Fei-Yi-Shen Formula in Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology Analysis and Molecular Docking Validation

BioMed Research International ◽

10.1155/2020/9105972 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Longchuan Wu ◽

Yu Chen ◽

Jiao Yi ◽

Yi Zhuang ◽

Lei Cui ◽

...

Keyword(s):

Molecular Docking ◽

Mechanism Of Action ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Chronic Obstructive ◽

Biological Functions ◽

Active Ingredients ◽

Obstructive Pulmonary Disease ◽

The Core ◽

Target Network

Objective. To explore the mechanism of action of Bu-Fei-Yi-Shen formula (BFYSF) in treating chronic obstructive pulmonary disease (COPD) based on network pharmacology analysis and molecular docking validation. Methods. First of all, the pharmacologically active ingredients and corresponding targets in BFYSF were mined by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the analysis platform, and literature review. Subsequently, the COPD-related targets (including the pathogenic targets and known therapeutic targets) were identified through the TTD, CTD, DisGeNet, and GeneCards databases. Thereafter, Cytoscape was employed to construct the candidate component-target network of BFYSF in the treatment of COPD. Moreover, the cytoHubba plug-in was utilized to calculate the topological parameters of nodes in the network; then, the core components and core targets of BFYSF in the treatment of COPD were extracted according to the degree value (greater than or equal to the median degree values for all nodes in the network) to construct the core network. Further, the Autodock vina software was adopted for molecular docking study on the core active ingredients and core targets, so as to verify the above-mentioned network pharmacology analysis results. Finally, the Omicshare database was applied in enrichment analysis of the biological functions of core targets and the involved signaling pathways. Results. In the core component-target network of BFYSF in treating COPD, there were 30 active ingredients and 37 core targets. Enrichment analysis suggested that these 37 core targets were mainly involved in the regulation of biological functions, such as response to biological and chemical stimuli, multiple cellular life processes, immunity, and metabolism. Besides, multiple pathways, including IL-17, Toll-like receptor (TLR), TNF, and HIF-1, played certain roles in the effect of BFYSF on treating COPD. Conclusion. BFYSF can treat COPD through the multicomponent, multitarget, and multipathway synergistic network, which provides basic data for intensively exploring the mechanism of action of BFYSF in treating COPD.

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