BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model

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1、Chiuetal.BMCCancer(2015)15:962DOI10.1186/s12885-015-1970-xRESEARCHARTICLEOpenAccessBPIQ,anovelsyntheticquinolinederivative,inhibitsgrowthandinducesmitochondrialapoptosisoflungcancercellsinvitroandinzebrafishxenograftmodel1,7,8,9,10*1,101,1014,96Chien-ChihChiu

2、,Han-LinChou,Bing-HungChen,Kuo-FengChang,Chih-HuaTseng,YaoFong,537922*Tzu-FunFu,Hsueh-WeiChang,Chang-YiWu,Eing-MeiTsai,Shinne-RenLinandYeh-LongChenAbstractBackground:2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1,2-c]q

3、uinolin-11-one(BPIQ)isaderivativefrom6-arylindeno[1,2-c]quinoline.Ourpreviousstudyshowedtheanti-cancerpotentialofBPIQcomparedtoitstwoanaloguestopotecanandirinotecan.Inthestudy,theaimistoinvestigatethepotencyandthemechanismofBPIQagainstlungcancercells.Methods:

4、Bothinvitroandzebrafishxenograftmodelwereperformedtoexaminetheanti-lungcancereffectofBPIQ.Flowcytometer-basedassayswereperformedfordetectingapoptosisandcellcycledistribution.Westernblotassaywasusedfordetectingthechangesofapoptoticandcellcycle-associatedprotei

5、ns.siRNAknockdownassaywasperformedforconfirmingtheapoptoticroleofBim.Results:Bothinvitroandzebrafishxenograftmodeldemonstratedtheanti-lungcancereffectofBPIQ.BPIQ-inducedproliferativeinhibitionofH1299cellswasachievedthroughtheinductionofG2/M-phasearrestandapop

6、tosis.TheresultsofWesternblotshowedthatBPIQ-inducedG2/M-phasearrestwasassociatedwithamarkeddecreaseintheproteinlevelsofcyclinBandcyclin-dependentkinase1(CDK1).Theup-regulationofpro-apoptoticBad,Bimanddown-regulationofpro-survivalXIAPandsurvivinwasobservedfoll

7、owingBPIQtreatment.Conclusions:BPIQ-inducedanti-lungcancerisinvolvedinmitochondrialapoptosis.BPIQcouldbeapromisinganti-lungcancerdrugforfurtherapplications.Keywords:Indeno[1,2-c]quinolinequinoline,BPIQ,Lungcancer,Apoptosis,Polyploidy,ZebrafishxenograftBackgro

8、undchemotherapeuticresistancecontributetothelowsur-Lungcancerisoneoftheleadingmalignanciesworld-vivalrateofNSCLCpatients[3].wide,andnon-smallcelllungcancer(NSCLC)accountsQuinolineringwasf