Garcinone e induces apoptosis and inhibits migration and invasion in ovarian cancer cells

Xiao Huang Xu, Qian Yu Liu, Ting Li, Jian Lin Liu, Xin Chen, Li Huang, Wen An Qiang, Xiuping Chen, Yitao Wang, Li Gen Lin*, Jin Jian Lu

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Ovarian cancer remains the most lethal gynecological malignant tumor. In this study, 24 xanthones were isolated and identified from the pericarps of mangosteen (Garcinia mangostana), and their anti-proliferative activities were tested in ovarian cancer cells. Garcinone E (GE) was found to exhibit excellent anti-proliferative effects among the tested xanthones. It significantly inhibited the proliferation in HEY, A2780, and A2780/Taxol cells as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, Hoechst 33342 staining, annexin V/PI staining, and JC-1 staining. It induced endoplasmic reticulum (ER) stress and activated the protective inositol-requiring kinase (IRE)-1α pathway. Knocking down IRE-1α further activated the caspase cascade and caused an increase in cell death. Moreover, GE eliminated the migratory ability of HEY cells by reducing the expression of RhoA and Rac. It also blocked the invasion, which might be related to downregulation of matrix metalloproteinases (MMPs), i.e., MMP-9 and MMP-2, and upregulation of tissue inhibitors of metalloproteinase (TIMP) -1 and TIMP-2. In summary, GE exerts anticancer activities by inducing apoptosis and suppressing migration and invasion in ovarian cancer cells, which indicates its therapeutic potential for ovarian cancer.

Original languageEnglish (US)
Article number10718
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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    Xu, X. H., Liu, Q. Y., Li, T., Liu, J. L., Chen, X., Huang, L., Qiang, W. A., Chen, X., Wang, Y., Lin, L. G., & Lu, J. J. (2017). Garcinone e induces apoptosis and inhibits migration and invasion in ovarian cancer cells. Scientific reports, 7(1), [10718]. https://doi.org/10.1038/s41598-017-11417-4