Background: Xanthones are a class of heterocyclic natural products, which are promising sources of
anti-cancer leads. Phomoxanthone B (PXB) and Phomoxanthone A(PXA)are xanthone dimers. PXA is wellstudied
as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus
Phomopsis sp. By254.
Objective: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast
cancer MCF7 cell line.
Methods: Apoptosis, cell cycle, proliferation, invasion, and migration assays were used to assess the anti-tumor
activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7
Results: PXB showed cytotoxicity towards a variety of tumor cells, especially MCF7 cells. PXB inhibited the
migration and invasion, arrested cell cycle at G2/M phase, and induced apoptosis associated with caspase-3
activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways
related to tumorigenesis, metabolisms, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome
analysis revealed that PXB upregulated pro-survival signal pathways, such as MAPK, PI3K-AKT, and STAT3
pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3, and XAF1, which
may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative
phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a
potential unfavorable prognostic marker for ER-positive breast cancer.
Conclusion: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast