Napieralski, RudolfColling, ChristophHonert, KatjaKrueger, AchimSchmitt, ManfredKiechle, Marion2022-01-072022-01-072011-12Arı, F. vd. (2011). "Modulation of protein expression levels and DNA methylation status of breast cancer metastasis genes by anthracycline-based chemotherapy and the demethylating agent decitabine". Cell Biochemistry and Function, 29(8), 651-659.0263-64841099-0844https://doi.org/10.1002/cbf.1801https://onlinelibrary.wiley.com/doi/10.1002/cbf.1801http://hdl.handle.net/11452/23937Epigenetic drugs are promising add-ons to cancer treatment; still, adverse effects concerning tumour promotion have been reported occasionally. In this in vitro study, we investigated the effect of combination treatment of decitabine with anthracycline-based chemotherapy [5-fluorouracil plus epirubicine plus cyclophosphamide (FEC)] on viability and metastatic activity of breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). The effect of decitabine and its combined treatment with FEC on viability of both cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and adenosine triphosphate (ATP) cell survival assays. DNA methylation specific real-time polymerase chain reaction (PCR) (Methylight (R)) was employed to document the methylation status of the metastasis-relevant urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-I (PAI-1) genes. Additionally, protein expression levels of uPA and PAI-1 were determined using enzyme-linked immunosorbent assays. Invasion capacity of cells was assayed using Matrigel (R) invasion assay. Decitabine lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not affected. Decitabine did not augment FEC-mediated cytotoxicity in both cell lines. In MCF-7 cells, methylation of the uPA and PAI-1 gene promoter was significantly reduced by decitabine or decitabine plus FEC. Protein levels of uPA and PAI-1 were induced by all treatments. Decitabine significantly induced the invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased invasion capacity of MDA-MB-231. Our results suggest differential effects of single-dose decitabine and its combination with FEC on the metastatic capacity and survival of breast cancer cell lines endowed with different metastatic behaviour.eninfo:eu-repo/semantics/closedAccessBiochemistry & molecular biologyCell biologyApoptosisBreast cancerDecitabineDNA methylationM30-antigenPAI-1UPAUrokinase upa promoterPlasminogen-activatorLuminescence assayClinical utilityTumor invasionInhibitorPai-1HypomethylationEpigeneticsRelevanceAnthracyclinesAntineoplastic combined chemotherapy protocolsAzacitidineBreast neoplasmsCell line, tumorDNA methylationFemaleGene expression regulation, neoplasticHumansNeoplasm iInvasivenessPlasminogen activator inhibitor 1Urokinase-type plasminogen activatorArticle0002976324000052-s2.0-8305519449065165929821887697Biochemistry & molecular biologyCell biologyUrokinase; Urokinase Plasminogen Activator Receptors; Plasminogen3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide5 aza 2' deoxycytidineAdenosine triphosphateAnthracyclineCyclophosphamideEpirubicinEstrogen receptorFluorouracilPlasminogen activator inhibitor 1UrokinaseApoptosisArticleBreast cancerCancer chemotherapyCancer inhibitionCancer invasionCell activityCell survivalCell viabilityControlled studyCytotoxicityDNA methylationDrug effectDrug sensitivityHumanHuman cellIn vitro studyMetastasisPriority journalProtein analysisProtein contentProtein expressionSingle drug dose