Karabulut B.Karaca B.Atmaca H.Kisim A.Uzunoglu S.Sezgin C.Uslu R.2024-07-222024-07-22201115734978http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/18177We report that all-trans retinoic acid (ATRA) in combination with zoledronic acid has strong synergistic cytotoxic and apoptotic effects against human hormone- and drug-refractory prostate cancer cells, PC-3 and DU-145, in a time- and dose-dependent manner. We further investigated the effect of the combination treatment on the apoptotic process by both oligoarray and protein array analysis in DU-145 cells, in which the drug combination shows much more strong synergistic effects, as compared to PC-3 cells. Moreover, we have also performed real time-PCR array analysis to validate oligoarray results. We demonstrated that the combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in human androgen-and drug refractory prostate cancer cells DU-145, at either transcriptional or translational levels. While expression of proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), Bad, Bax, Fas, FADD are induced with the exposure of the combination, expression of antiapoptotic genes or proteins such as members of inhibitor apoptosis family (IAPs), MCL-1, LTBR, p53 and bcl-2 are reduced. Because this novel combination treatment has fewer side effects than is generally the case with conventional cytotoxic agents, this regimen may be a good option for treatment of elderly prostate cancer patients. © 2010 Springer Science+Business Media B.V.EnglishAntineoplastic AgentsApoptosisApoptosis Regulatory ProteinsCaspase 3Caspase 7Cell DeathCell Line, TumorCell ProliferationCell SurvivalDiphosphonatesDNA FragmentationDose-Response Relationship, DrugDrug SynergismGene Expression Regulation, NeoplasticHormonesHumansImidazolesMaleProstatic NeoplasmsReceptors, Tumor Necrosis FactorReproducibility of ResultsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTime FactorsTretinoinIntracisternal A-particlescaspase 3caspase 7cytochrome cFas associated death domain proteinFas ligandheme oxygenase 2livinlymphotoxin beta receptorprotein BADprotein Baxprotein bcl 2protein mcl 1protein p53retinoic acidsecond mitochondrial activator of caspasesurvivintumor necrosis factor receptortumor necrosis factor receptor superfamilyunclassified drugX linked inhibitor of apoptosiszoledronic acidapoptosisarticlecancer cell culturecancer inhibitioncell proliferationcell viabilitycontrolled studycytotoxicityDNA fragmentationdose responsedrug potentiationenzyme activationenzyme activityhumanhuman cellmaleprostate cancerprotein expressionreal time polymerase chain reactionArticle10.1007/s11033-010-0102-6