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      Curcumin Has Anti-Proliferative and Pro-Apoptotic Effects on Tongue Cancer in vitro: A Study with Bioinformatics Analysis and in vitro Experiments

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          Abstract

          Purpose

          This study focused on the mechanism underlying the therapeutic effect of curcumin against tongue cancer (TC).

          Methods

          Target genes of TC and curcumin were identified, respectively. Three datasets of TC from Gene Expression Omnibus were included, and then the differentially expressed genes were collected. After combing the data from The Cancer Genome Atlas, bioinformatics analyses were performed to investigate hub genes in terms of the functions and correlations. The proliferation and migration of TC cells were evaluated with CCK-8 assay and scratch wound healing assay, respectively. Cell apoptosis was evaluated by TUNEL assay, flow cytometry and Western blot. Cell cycle was determined by flow cytometry.

          Results

          In this study, 15 hub genes were identified (TK1, TDRD3, TAGLN2, RNASEH2A, PDE2A, NCF2, MAP3K3, GPX3, GPD1L, GBP1, ENO1, CAT, ALDH6A1, AGPS and ACACB). They were mainly enriched in oxygen-related processes, such as oxidation-reduction process, reactive oxygen species metabolic process, hydrogen peroxide catabolic process, oxidoreductase activity and Peroxisome-related pathway. The expression levels of hub gene mRNAs were positively correlated with each other’s expression levels. None of the hub genes was correlated with prognosis ( P > 0.05). Curcumin significantly inhibited CAL 27 cell proliferation and migration ( P < 0.05), but significantly promoted cell apoptosis ( P < 0.05).

          Conclusion

          Curcumin has potential therapeutic effect on treating TC by suppressing cell proliferation and migration, as well as promoting apoptosis through modulating oxygen-related signaling pathways.

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          Most cited references 28

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          Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.

          Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
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            Multiple biological activities of curcumin: a short review.

            Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.
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              PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach

              In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in the drug discovery pipeline. When the 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and small molecule probes. Pharmacophore, which is the spatial arrangement of features essential for a molecule to interact with a specific target receptor, is an alternative method for achieving this goal apart from molecular docking method. PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules (drugs, natural products or other newly discovered compounds with unidentified binding targets) using pharmacophore mapping approach. PharmMapper hosts a large, in-house repertoire of pharmacophore database (namely PharmTargetDB) annotated from all the targets information in TargetBank, BindingDB, DrugBank and potential drug target database, including over 7000 receptor-based pharmacophore models (covering over 1500 drug targets information). PharmMapper automatically finds the best mapping poses of the query molecule against all the pharmacophore models in PharmTargetDB and lists the top N best-fitted hits with appropriate target annotations, as well as respective molecule’s aligned poses are presented. Benefited from the highly efficient and robust triangle hashing mapping method, PharmMapper bears high throughput ability and only costs 1 h averagely to screen the whole PharmTargetDB. The protocol was successful in finding the proper targets among the top 300 pharmacophore candidates in the retrospective benchmarking test of tamoxifen. PharmMapper is available at http://59.78.96.61/pharmmapper.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                04 February 2020
                2020
                : 14
                : 509-518
                Affiliations
                [1 ]Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University , Nanning, People’s Republic of China
                [2 ]Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University , Nanning, People’s Republic of China
                Author notes
                Correspondence: Haoyu Li Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University , 6 Shuangyong Road, Nanning530021, Guangxi Zhuang Autonomous Region, People’s Republic of China Email med.dr.lihy@gmail.com
                Article
                237830
                10.2147/DDDT.S237830
                7007779
                © 2020 Ma 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).

                Page count
                Figures: 8, Tables: 1, References: 39, Pages: 10
                Categories
                Original Research

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