Selective Targeting of Tumorigenic Cancer Cell Lines by Microtubule Inhibitors 英文参考文献.docVIP

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Selective Targeting of Tumorigenic Cancer Cell Lines by Microtubule Inhibitors 英文参考文献.doc

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SelectiveTargetingofTumorigenicCancerCellLinesby MicrotubuleInhibitors NewajM.Abdullah1,GusR.Rosania1,3*,KerbyShedden2,3 * 1Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan, United States of America, 2Department of Statistics, UniversityofMichigan,AnnArbor,Michigan,UnitedStatesofAmerica,3MichiganAllianceforCheminformaticsExploration(MACE),AnnArbor,Michigan,UnitedStatesof America Abstract Foranticancerdrugtherapy,itiscriticaltokillthosecellswithhighesttumorigenicpotential,evenwhentheycomprisea relatively small fraction of the overall tumor cell population. We have used the established NCI/DTP 60 cell line growth inhibition assay as a platform for exploring the relationship between chemical structure and growth inhibition in both tumorigenicandnon-tumorigeniccancercelllines.Usingexperimentalmeasurementsof‘‘takerate’’inectopicimplantsasa proxy for tumorigenic potential, we identified eight chemical agents that appear to strongly and selectively inhibit the growthofthemosttumorigenic celllines.Biochemicalassaydataandstructure-activityrelationships indicatethatthese compoundsactbyinhibitingtubulinpolymerization.Yet,theiractivityagainsttumorigeniccelllinesismoreselectivethan that of the other microtubule inhibitors in clinical use. Biochemical differences in the tubulin subunits that make up microtubules,ordifferencesinthefunctionofmicrotubulesinmitoticspindleassemblyorcelldivisionmaybeassociated withtheselectivityofthesecompounds. Citation: AbdullahNM,RosaniaGR,SheddenK(2009)SelectiveTargetingofTumorigenic CancerCellLinesbyMicrotubuleInhibitors.PLoSONE4(2):e4470. doi:10.1371/journal.pone.0004470 Editor:WinstonHide,UniversityoftheWesternCape,SouthAfrica ReceivedAugust8,2008;AcceptedNovember28,2008;PublishedFebruary13,2009 Copyright: ? 2009 Abdullah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andrep