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

怒江藤黄中的抗肿瘤黄酮类化合物通过PARP、PI3K/AKT/mTOR和MAPK/ERK信号通路抑制人卵巢癌细胞增殖并诱导其凋亡

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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.

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