title: 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.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chi
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Minliang
authors.initials: M
authors.lastname: Kuo
authors.affiliation: National Institute of Cancer Research, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Alan Yueh-Luen
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D005260:Female; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D032101:Murraya / Q000737:chemistry*; D009362:Neoplasm Metastasis; D051381:Rats; D014859:Warfarin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D014859:Warfarin