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      Drug Design, Development and Therapy (submit here)

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      Investigation of Inhibition Effect of Gossypol-Acetic Acid on Gastric Cancer Cells Based on a Network Pharmacology Approach and Experimental Validation


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          Gastric cancer (GC) is one of the major public health problems worldwide with high morbidity and mortality. Nowadays, traditional medicine may hold promise for the treatment of cancers. Gossypol-acetic acid (GAA) is a male contraceptive agent that shows anti-tumor effects on multiple types of cancers. However, whether GAA would inhibit the progression of GC remained unclear.


          The potential targets of GAA were predicted by the Pharmmapper software and GC-related genes were obtained from the GeneCard database. The “GC-targets-GAA” network was constructed using the Cytoscape software. The PPI analysis of intersection genes was performed using the String software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID software to explore the potential mechanism underlying the regulatory role of GAA in GC. The MTS test, plate cloning test, cell cycle and apoptosis assays were used to verify the function of GAA in GC.


          Ten hub genes related to cell cycle progression and apoptosis were identified. Many cancer-related signaling pathways were visualized by the Cytoscape software. Among them, the PI3K-Akt signaling pathway was the highest-ranked pathway. The MTS test and plate cloning test showed that GAA inhibited the proliferation of GC cells. The cell cycle and apoptosis assays showed that GAA induced G1 phase cell cycle arrest and apoptosis in GC cells.


          Our study demonstrated the anti-tumor effect of GAA on GC through multiple targets and signaling pathways. These results provided a theoretical basis for further investigation of GAA in preclinical and clinical studies, and suggested the potential use of GAA as a novel therapeutic agent for the treatment of GC.

          Most cited references19

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          PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery

          The discovery of the nitric oxide/cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of PDE5 have been the first-line therapy for erectile dysfunction (ED). The success of sildenafil in the treatment of ED stimulated research in the field of PDE5 inhibition and led to many new applications, such as treatment of lower urinary symptoms, and pulmonary arterial hypertension, which are now approved indications. However, PDE5 inhibitors have also been used in several other disorders not discussed in this review, and the fields of clinical use are increasing. In the present review, the pharmacological basis of the NO/cGMP pathway and the rationale and clinical use of PDE5 inhibitors in different diseases are discussed.
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            Complex roles of the old drug aspirin in cancer chemoprevention and therapy

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              Systematic elucidation of the mechanism of geraniol via network pharmacology

              Background Geraniol is an acyclic monoterpene alcohol, which is extracted from the ethereal oils of aromatic plants. A systematic analysis of its mechanism of action has not yet been carried out. Methods In this study, the druggability of geraniol was assessed via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of geraniol were identified using the Comparative Toxicogenomics Database (CTD). Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using WebGestalt. Drug-target-pathway networks were constructed using Cytoscape to give a visual view. Results Our findings showed that geraniol has superb druggability with 38 putative identified target genes. GO, KEGG, and network analyses revealed that these targets were associated with cancer, inflammatory immunoreactions, and other physiological processes. Conclusion Geraniol is predicted to target multiple proteins and pathways that shape a network which can exert systematic pharmacological effects.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                07 September 2020
                : 14
                : 3615-3623
                [1 ]The Second Department of Surgery, The Fourth Hospital of Hebei Medical University , Shijiazhuang 050011, People’s Republic of China
                [2 ]Department of Medical Oncology, The Fourth Hospital of Hebei Medical University , Shijiazhuang 050011, People’s Republic of China
                [3 ]The Third Hospital of Hebei Medical University , Shijiazhuang 050011, People’s Republic of China
                [4 ]The Fourth Hospital of Hebei Medical University , Shijiazhuang 050011, People’s Republic of China
                Author notes
                Correspondence: Guiying Wang Email wangguiyingtgzy@163.com
                © 2020 Liu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 02 April 2020
                : 08 August 2020
                Page count
                Figures: 8, References: 20, Pages: 9
                Original Research

                Pharmacology & Pharmaceutical medicine
                gastric cancer,gc,gossypol-acetic acid,gaa,network pharmacology,proliferation


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