Capsaicin Displays Anti-Proliferative Activity against Human Small Cell Lung Cancer in Cell Culture and Nude Mice Models via the E2F Pathway 英文参考文献.docVIP

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Capsaicin Displays Anti-Proliferative Activity against Human Small Cell Lung Cancer in Cell Culture and Nude Mice Models via the E2F Pathway 英文参考文献.doc

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Capsaicin Displays Anti-Proliferative Activity against Human Small Cell Lung Cancer in Cell Culture and Nude Mice Models via the E2F Pathway 英文参考文献

CapsaicinDisplaysAnti-ProliferativeActivityagainst HumanSmallCellLungCancerinCellCultureandNude MiceModelsviatheE2FPathway KathleenC.Brown1.,TedR.Witte2.,W.ElaineHardman2,HaitaoLuo3,YiC.Chen3,A.BettsCarpenter4, JamieK.Lau1,PiyaliDasgupta1* 1DepartmentofPharmacology,PhysiologyandToxicology,JoanC.EdwardsSchoolofMedicine,MarshallUniversity,Huntington,WestVirginia,UnitedStatesofAmerica, 2Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, United States of America, 3DepartmentofBiology,Alderson-BroaddusCollege,Phillipi,WestVirginia,UnitedStatesofAmerica,4DepartmentofAnatomyandPathology,JoanC.EdwardsSchool ofMedicine,MarshallUniversity,Huntington,WestVirginia,UnitedStatesofAmerica Abstract Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti- proliferativeactivityinprostateandepidermoidcancerinvitro.However,theanti-proliferativeactivityofcapsaicinhasnot beenstudiedinhumanSCLCs.Thepresentmanuscriptfillsthisvoidofknowledgeandexplorestheanti-proliferativeeffect ofcapsaicininSCLCinvitroandinvivo. Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activityinfourhumanSCLCcelllines.Furthermore,capsaicinpotentlysuppressedthegrowthofH69humanSCLCtumorsin vivoasascertainedbyCAMassaysandnudemicemodels.Thesecondpartofourstudyattemptedtoprovideinsightinto molecularmechanismsunderlyingtheanti-proliferativeactivityofcapsaicin.Wefoundthattheanti-proliferativeactivityof capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase,cdc25Aandcdc6,bothatmRNAandproteinlevels.ThetranscriptionfactorE2F4mediatedtheanti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodolog