NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo 英文参考文献.docVIP

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NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo 英文参考文献.doc

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NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo 英文参考文献

NAHA,aNovelHydroxamicAcid-Derivative,Inhibits GrowthandAngiogenesisofBreastCancerInVitroand InVivo JiahuaJiang1,AnitaThyagarajan-Sahu1,ViktorKrchnˇa′k2,AndrejJedinak1,GeorgeE.Sandusky3, DanielSliva1,4,5 * 1CancerResearchLaboratory,MethodistResearchInstitute,IndianaUniversityHealth,Indianapolis,Indiana,UnitedStatesofAmerica, 2DepartmentofChemistryand Biochemistry,UniversityofNotreDame,NotreDame,Indiana,UnitedStatesofAmerica,3DepartmentofPathology,SchoolofMedicine,IndianaUniversity,Indianapolis, Indiana,UnitedStatesofAmerica,4DepartmentofMedicine,SchoolofMedicine,IndianaUniversity,Indianapolis,Indiana,UnitedStatesofAmerica,5IUSimonCancer Center,SchoolofMedicine,IndianaUniversity,Indianapolis,Indiana,UnitedStatesofAmerica Abstract Background: We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro- benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHAagainsthighlyinvasivehumanbreastcancercellsMDA-MB-231invitroandinvivo. Methodology/Principal Findings: Cell growth was evaluated by MTT and soft agar assays. Protein expression was determinedbyDNAmicroarrayandWesternblotanalysis.Metastaticpotentialwasevaluatedbycelladhesion,migration, invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expressionofCdk2andCDC20proteins.NAHAinhibitedcelladhesion,migration,andinvasionthroughthesuppressionof secretion of uPA. NAHA suppressed secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of humanaorticendothelialcells(HAECs).Finally,NAHAat50mg/kgwasnottoxicanddecreasedtumorvolumeandtumor weight in vivo. This suppression of tumor growth was associated with the inhibition of mitotic figures and induction of apoptosis,andthereductionofCD31andVEGFpositivecellsintumors. Con