Anti-Tumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

Author(s): Chuan Chen, Ziyue Zhao, Qian Dong, XueHui Gao, Huibin Xu, Runlei Yang, JianChun Qin*, Duqiang Luo*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 14 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

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 cells.

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 cancer treatment.

Keywords: Phomoxanthone, RNA-Seq, MCF7 cells, MAPK, PI3K-AKT, JAK-STAT.

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 14
Year: 2021
Published on: 24 November, 2020
Page: [1825 - 1834]
Pages: 10
DOI: 10.2174/1871520620999201124215511
Price: $65

Article Metrics

PDF: 323