Study On The Anticancer Effect And Molecular Mechanism Of Eupatorium Adenophorum Spreng.

Objective: To adequately utilize well-known noxious invasive plant,Eupatorium adenophorum Spreng.(EA),we investigated the anticancer activities of extracts derived from EA and explored their toxicologic impacts and the potential molecular mechanisms.Method: MTT assay,Hoechst 33258 stainning,flow cytometry,immunoblot and IHC were performed to analysis the anticancer activities of the extracts and the potential mechanisms of active site.Antioxidant kit and enzyme kinetic were performed to investigate antioxidant and anti-inflammation activities.HepG2-bearing nude mouse model were established and treated i.p.with the extracts for about 4 weeks.Tumor size was measured every 4 days.Three weeks later,mice were sacrificed and transplanted tumors were removed for immunoblot.Results: 1.The extracts derived from E.adenophorum Spreng.showed anti-HCC effect.Essential oil(EAEO)was more effective than the other extracts.GC-MS analysis showed that there were 18 different compounds in EAEO,representing 96.33% of the total oil,in which 11 principles belonged to sesquiterpenoids.2.Results showed that EAEO dose-dependently enhanced inhibition rates of HepG2,Hep3 B and SMMC-7721 cells,but no distinct antiproliferative activity against L02 was observed.3.Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle,respectively.Moreover,EAEO promoted in vitro HCC cell apoptosis.4.EAEO treatment significantly reduced the ratio of Bcl-2/Bax,while increased the expressions of cleaved caspase-9 and caspase-3 in a dose-dependent manner.EAEO-treatment declined the expression of Grp78 and increased the expressions of cleaved caspase-12 and-7.EAEO dose-dependently repressed the basal phosphorylation of STAT3 at Tyr705 and Ser727 but did not inhibit protein levels of total STAT3.Conclusion: EAEO remains great potential for development and application with suppressing hepatocellular carcinoma cells via activation of the mitochondrial apoptotic pathway,as well as exhibited antioxidant and anti-inflammation activities.