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

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
• xanthone
• ovarian cancer; OC
• molecular docking
• apoptosis

Data Sharing Statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no competing interests.