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

BackgroundOvarian cancer (OC) is a serious public health concern in the world. It is important to develop novel drugs to inhibit OC.PurposeThis study investigated the isolation, elucidation, efficiency, molecular docking, and pharmaceutical mechanisms of xanthones isolated from Garcinia nujiangensis.MethodsXanthones 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.ResultsBioassay-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.ConclusionIn conclusion, isojacareubin (2) might be a potential drug for the treatment of OC.