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.