Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives

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.

Incorporating Stories of Sedatives, Spoiled Sweet Clover Hay, and Plants from the Amazon Rainforest into a Pharmaceutical Chemistry Course To Engage Students and Introduce Drug Design Strategies

“…As a real example of how HPLC can be used to separate and analyze samples from natural origins, a semi-preparative HPLC method for the isolation of warfarin and coumarin-like molecules from a medicinal plant, Murraya paniculata was presented 25 . The isolated molecules were characterized by means of MS. Next, the isolated compounds were tested as chemopreventive agents for metastatic cancer in colon cancer cell lines.…”

Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention

“…We also found that the extracts from traditional abortion Chinese medicinal plants Murray paniculata and Achyranthes bidentate produced efficient CTC-based metastatic chemoprevention [17][18][19][20][21][22][23]. Although today CTCs are regarded as the root cause of cancer metastases [24], and CTCs separation and identification technologies are very mature [25],drugs for specifically targeting-andkilling CTCs without producing significant side effects are very difficultly to be developed due to the rareness of CTCs in blood.…”

Embedding Similarities Between Embryos And Circulating Tumor Cells: Fundamentals of Abortifacients Used For Cancer Metastasis Chemoprevention

“…Although its cancer chemotherapeutic trials were not successful as most of the anticancer drugs did, we found and demonstrated that mifepristone and its prime metabolite metapristone were safe and effective in our CTC-based metastatic chemopreventive studies(8-16). We also found that the extracts from traditional abortion Chinese medicinal plants Murray paniculata and Achyranthes bidentate produced e cient CTC-based metastatic chemoprevention (17)(18)(19)(20)(21)(22)(23). Although today CTCs are regarded as the root cause of cancer metastases (24), and CTCs separation and identi cation technologies are very mature (25),drugs for speci cally targeting-and-killing CTCs without producing signi cant side effects are very di cultly to be developed due to the rareness of CTCs in blood.…”