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

• Main Authors: Tang Z, Lu L, Xia Z
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: Drug Design, Development and Therapy
• Subjects: garcinia nujiangensis; xanthone; ovarian cancer; molecular docking; apoptosis
• Online Access: https://www.dovepress.com/anti-tumor-xanthones-from-garcinia-nujiangensis-suppress-proliferation-peer-reviewed-article-DDDT

Zhongyan Tang,1,* Lihua Lu,2,* Zhengxiang Xia3 1Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai 201508, People’s Republic of China; 2Department of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 3Department of Pharmacy, School & Hospital of Stomatology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji University, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengxiang Xia Tel [phone]Email [e-mail]: 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-C18), 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.Keywords: Garcinia nujiangensis, xanthone, ovarian cancer; OC, molecular docking, apoptosis