title: The paradigm-shifting idea and its practice: from traditional abortion Chinese medicine Murraya paniculata to safe and effective cancer metastatic chemopreventives.
abstract: Recent large epidemiological studies demonstrated benefit of oral contraceptives in reducing cancer risk, and our analysis also showed molecular and cellular similarities between embryo implantation and CTCs adhesion-invasion to endothelium. We here hypothesize that abortion traditional Chinese medicine (TCM) may serve well for pre-metastatic chemoprevention. To test the hypothesis, we selected the safe and well-known abortifacient TCM Murraya paniculata and identified a most-promising extracted fraction G (containing flavonoids and coumarins) from its many raw ethanol/dichloromethane extracts by using the bioactivity-guided fast screen assay. G showed free radical scavenging effect, and specifically inhibited both embryo implantation to human endometrial bed and cancer HT29 cells to human endothelium in a concentration-dependent manner (1-30 μg/mL) without significant cytotoxicity demonstrated by its high adhesion inhibition ratio. The inhibition may result from its down-regulation on expression of integrin β1 and α6, and CD44 on HT29 cells, as well as E-selectin on endothelial cells. Furthermore, G inhibited invasion and migration of HT29 cells. Pretreatment followed by one-month oral administration of G to the immunocompetent mice inoculated with mouse melanoma cells produced significant inhibition on lung metastasis without marked side effects. Collectively, this paradigm-shifting study provides, for the first time, a new strategy to discover safe and effective pre-metastatic chemopreventives from abortion TCM.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, 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, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, 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, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
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: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000019:Abortifacient Agents / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018890:Chemoprevention / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D019073:HT29 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008516:Medicine, Chinese Traditional / Q000379:methods* / Q000639:trends; D008546:Melanoma, Experimental / Q000473:pathology / Q000517:prevention & control; D008810:Mice, Inbred C57BL; D032101:Murraya / Q000737:chemistry*; D010936:Plant Extracts / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000019:Abortifacient Agents; D010936:Plant Extracts
keywords: Murraya paniculata; cancer metastatic chemoprevention; cell adhesion molecules; circulating tumor cells; traditional abortion Chinese medicine