Description
Amsacrineisananticancerchemotherapeuticacridinederivativethatisclinicallyusedtotreatacutemyelogenousleukemia(AML).AmsacrineactsasaDNAintercalator,bindingATbasepairs;thisinhibitstheactivityoftopoisomeraseII,preventingDNArepair.Inleukemiacells,amsacrinedecreasesexpressionofmatrixmetalloproteinases2and9(MMP2/9),inhibitingcellinvasion.ThismodulationofMMP2/9expressioniscausedbyincreasesinROSandactivationofp38MAPKandJNK,whichincreaseslevelsofproteinphosphatase2A(PP2A),anegativeregulatorofMMPactivity.Invitro,amsacrineinhibitshumanEther-a-go-go-RelatedGene(hERG)K+channels,causingpotentialprolongationoftheQTinterval.
References
LiuWH,ChenYJ,ChienJH,etal.Amsacrinesuppressesmatrixmetalloproteinase-2(MMP-2)/MMP-9expressioninhumanleukemiacells.JCellPhysiol.2013Oct7.Epubaheadofprint.PMID:24122234.
JangirDK,DeySK,KunduS,etal.AssessmentofamsacrinebindingwithDNAusingUV-visIBLe,circulardichroismandRamanspectroscopictechniques.JPhotochemPhotobiolB.2012Sep3;114:38-43.PMID:22677564.
ThomasD,HammerlingBC,WuK,etal.InhibitionofcardiacHERGcurrentsbytheDNAtopoisomeraseIIinhibitoramsacrine:modeofaction.BrJPharmacol.2004Jun;142(3):485-94.PMID:15148258.
RobinsonMJ,OsheroffN.StABIlizationofthetopoisomeraseII-DNAcleavagecomplexbyantineoplasticdrugs:inhibitionofenzyme-mediatedDNAreligationby4"-(9-acridinylamino)methanesulfon-m-anisidide.Biochemistry.1990Mar13;29(10):2511-5.PMID:2159323.
