The paradigm-shifting idea and its practice: from traditional abortion Chinese medicine Murraya paniculata to safe and effective cancer metastatic chemopreventives
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Zhou Jiang1,2,*, Yaqiong Pang1,*, Xiaobo Yu1,*, Suxia Zhou1, Jun Qian1, Ning Zheng1, Haiyan Dong1, Qing Shi1, Minliang Kuo3, Lee Jia1,2
1Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, China
2Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, China
3Graduate Institute of Biomedical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
*These authors contributed equally to this work
Lee Jia, e-mail: [email protected]
Keywords: cancer metastatic chemoprevention, circulating tumor cells, cell adhesion molecules, traditional abortion Chinese medicine, Murraya paniculata
Received: October 24, 2015 Accepted: February 05, 2016 Published: March 05, 2016
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.
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