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

Zhongyan Tang; Lihua Lu; Zhengxiang Xia

doi:10.2147/DDDT.S258811

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

Drug Des Devel Ther. 2020 Sep 25:14:3965-3976. doi: 10.2147/DDDT.S258811. eCollection 2020.

Authors

Zhongyan Tang^#¹, Lihua Lu^#², Zhengxiang Xia³

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.

^# Contributed equally.

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-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; apoptosis; molecular docking; ovarian cancer; OC; xanthone.

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Female
Garcinia / chemistry*
Humans
MAP Kinase Signaling System / drug effects
Molecular Docking Simulation
Molecular Structure
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Phosphatidylinositol 3-Kinases / metabolism
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism
Structure-Activity Relationship
TOR Serine-Threonine Kinases / antagonists & inhibitors
TOR Serine-Threonine Kinases / metabolism
Tumor Cells, Cultured
Xanthones / chemistry
Xanthones / isolation & purification
Xanthones / pharmacology*

Substances

Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Xanthones
Poly(ADP-ribose) Polymerases
MTOR protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases

Grants and funding

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).