Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives
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Updated: Mar 17, 2026
Quantitation of Endothelial Cell Adhesiveness In Vitro
Published on: June 18, 2015
Jingwei Shao1,2, Suxia Zhou1, Zhou Jiang1,2
1Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.
Abstract:
We recently defined cancer metastatic chemoprevention as utilizing safe and effective molecules to comprehensively prevent the spark of activation-adhesion-extravasation-proliferation metastatic cascade caused by circulating tumor cells (CTCs). The strategy focuses on preventing the most important starting point of the cascade. We identified an extract from a well-known medical plant Murraya paniculata, which inhibited both embryonic implantation to human endometrium as traditionally-used for abortion and CTC adhesion to human endothelium. Here, we separated and characterized five coumarin-containing components (Z1-Z5) from the botanic extract. Flow cytometry revealed that within 1-100 μg/mL, Z3 and Z5 down-regulated EpCAM expression in human colon HCT116, whereas, Z1 and Z2 did oppositely. Warfarin and Z1-Z5 component mixture (CM) also down-regulated EpCAM expression. The down-regulation of EpCAM by Z3, Z5, CM and warfarin was confirmed by western blotting, and caused inhibition on adhesion of cancer cells to human endothelial cells. Rat coagulation study showed that warfarin prolonged prothrombin time, whereas, Z3 did not. The present studies revealed that, for the first time, warfarin and coumarin-like components Z3, Z5 and CM from Murraya paniculata could directly inhibit EpCAM-mediated cell-cell adhesion.
Insights
Murraya paniculata extracts, including coumarin components Z3 and Z5, inhibit cancer cell adhesion by down-regulating EpCAM expression. This discovery offers a novel strategy for cancer metastatic chemoprevention.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Cancer metastasis involves a cascade initiated by circulating tumor cells (CTCs).
- Cancer metastatic chemoprevention aims to inhibit this cascade using safe molecules.
- Murraya paniculata extract shows potential in preventing embryonic implantation and CTC adhesion.
Purpose of the Study:
- To isolate and characterize coumarin components from Murraya paniculata.
- To investigate the effect of these components on EpCAM expression and cancer cell adhesion.
- To evaluate the anti-metastatic potential of these compounds.
Main Methods:
- Extraction and separation of coumarin components (Z1-Z5) from Murraya paniculata.
- Flow cytometry and western blotting to assess EpCAM expression.
- In vitro assays to measure cancer cell adhesion to endothelial cells.
- Rat coagulation study to assess warfarin and Z3 safety.
Main Results:
- Components Z3 and Z5, along with the component mixture (CM) and warfarin, down-regulated EpCAM expression in HCT116 cells.
- Down-regulation of EpCAM correlated with inhibited cancer cell adhesion to endothelial cells.
- Warfarin prolonged prothrombin time, but Z3 did not, indicating a potentially safer profile.
Conclusions:
- Warfarin and coumarin-like components (Z3, Z5, CM) from Murraya paniculata inhibit EpCAM-mediated cell-cell adhesion.
- These compounds represent a novel approach to cancer metastatic chemoprevention.
- Z3 shows potential as a safe chemopreventive agent due to its lack of anticoagulant activity.
