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      Anti-Tumor Xanthones from Garcinia nujiangensis Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells

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          Abstract

          Background

          Ovarian cancer (OC) is a serious public health concern in the world. It is important to develop novel drugs to inhibit OC.

          Purpose

          This study investigated the isolation, elucidation, efficiency, molecular docking, and pharmaceutical mechanisms of xanthones isolated from Garcinia nujiangensis.

          Methods

          Xanthones were isolated, and purified by different chromatography, including silica gel, reversed-phase silica gel (ODS-C 18), and semipreparative HPLC, then identified by analysis of their spectral data. Three xanthones were estimated for their efficiency on the human OC cells HEY and ES-2. 2 was found to be the most potent cytotoxic xanthones of those tested. Further, its mechanisms of action were explored by molecular docking, cell apoptosis, and Western blotting analysis.

          Results

          Bioassay-guided fractionation of the fruits of Garcinia nujiangensis led to the separation of a new xanthone named nujiangexanthone G ( 1) and two known xanthones. Among these, isojacareubin ( 2) exhibited the most potent cytotoxic compound against the HEY and ES-2 cell lines. The analysis of Western blot suggested that 2 inhibited OC via regulating the PARP, PI3K/AKT/mTOR, and ERK/MAPK signal pathways in the HEY cell lines.

          Conclusion

          In conclusion, isojacareubin ( 2) might be a potential drug for the treatment of OC.

          Most cited references44

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          Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance

          Ovarian cancer (OC) is a lethal gynecological cancer. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation. Irregularities in the major components of the PI3K/AKT/mTOR signaling pathway are common in human cancers. Despite the availability of strong pre-clinical and clinical data of PI3K/AKT/mTOR pathway inhibitors in OC, there is no FDA approved inhibitor available for the treatment of OC. Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.
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            Multispecific drugs herald a new era of biopharmaceutical innovation

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              PARP inhibitors in ovarian cancer

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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
                25 September 2020
                2020
                : 14
                : 3965-3976
                Affiliations
                [1 ]Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University , Shanghai 201508, People’s Republic of China
                [2 ]Department of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030, People’s Republic of China
                [3 ]Department of Pharmacy, School & Hospital of Stomatology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji University , Shanghai 200072, People’s Republic of China
                Author notes
                Correspondence: Zhengxiang Xia Tel +8621-66315500 Email xzx5380537@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-9044-9180
                Article
                258811
                10.2147/DDDT.S258811
                7524179
                c950fbfc-3387-4990-9049-48c6df4ffe52
                © 2020 Tang 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).

                History
                : 30 April 2020
                : 21 August 2020
                Page count
                Figures: 9, Tables: 1, References: 47, Pages: 12
                Funding
                Funded by: Special subject for scientific research of Chinese Medicine from Shanghai Municipal Commission of Health and Family Planning;
                Award ID: 2018JP007
                This work was supported by the Special subject for scientific research of Chinese Medicine from Shanghai Municipal Commission of Health and Family Planning (No. 2018JP007).
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                garcinia nujiangensis,xanthone,ovarian cancer; oc,molecular docking,apoptosis

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