| Armillariamellea(Tricholomataceae)isamedicinalfungussymbioticwithChinesemedicinalherb“Tianma”(GastrodiaelataBlume).17compoundswiththesamesesquiterpenoidskeletonwereisolatedfrommyceliumofArmillariamellea,amongthem,7compoundsarenovel.All17compoundswereconfirmedwithanti-angiogenesisactivityandstrongcancercellcytotoxiceffectonhumanbreast,lungandcoloncancers,andleukemia.Amongthem,armillaridinshowedpotentialeffectonhumannon-smallcelllungcancer.ArmillaridindecreasedtheamountsofCdk2,Cdk4,CyclinD1andCyclinEthatresultedincellcyclearrestinginG1phaseinH460andA549cells.Italsoinducedapoptosisviaactivationofcaspase3and7butnotaffectedcaspase8and9.Theseeffectsmightparticipateincancercellcytotoxicityofarmillaridin.Besides,actinrearrangementandcytoskeletonalternationwerevisualizedunderconfocalmicroscopeafteramillaridintreatment.ImmunoblotassayrevealedasuppressionofRho/cdc25-LIMKpathwaybyamillaridin.TheseresultsindicatedthatamillaridindisruptedactinrearrangementthroughinhibitionofRho/cdc25-LIMKpathway.Animaltestsindicatedthatamillaridindose-dependentlyinhibitedinvivoangiogenesisandshowedsimilardose-dependenttumorregressioninhumanH460xenograftanimals.Therefore,weanticipatetoidentifyvaluableleadsfromArmillariamelleafordevelopmentofnewanticancerdrug. |