Atmaca H.Bozkurt E.Uzunoglu S.Uslu R.Karaca B.2024-07-222024-07-22201303784274http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/17180Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer. © 2013 Elsevier Ireland Ltd.EnglishApoptosisbcl-2-Associated X Proteinbcl-Associated Death ProteinBreast NeoplasmsCaspase 3Caspase 7Cell Line, TumorCytochromes cDioxolesFemaleGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMCF-7 CellsMitochondriaMitochondrial ProteinsReactive Oxygen SpeciesReceptors, TNF-Related Apoptosis-Inducing LigandTetrahydroisoquinolinescaspase 3cytochrome cdeath receptorepidermal growth factor receptor 2estrogen receptorprotein Baxprotein bcl xlreactive oxygen metabolitetrabectedintumor necrosis factor related apoptosis inducing ligand1,3 dioxolane derivativeBAD protein, humanBAX protein, humanCASP3 protein, humanCASP7 protein, humancaspase 3caspase 7cytochrome cDIABLO protein, humanmitochondrial proteinprotein BADprotein Baxreactive oxygen metabolitesignal peptidetetrahydroisoquinoline derivativeTNFRSF10A protein, humantrabectedintumor necrosis factor related apoptosis inducing ligand receptorantineoplastic activityapoptosisarticlebreast cancercell strain MCF 7concentration (parameters)controlled studycytotoxicityEcteinascidia turbinataenzyme metabolismgenotypehumanhuman cellmitochondrionpriority journalprotein expressionprotein foldingUrochordataapoptosisbreast tumordrug effectsfemalegene expression regulationgeneticsMCF 7 cell linemetabolismpathologytumor cell lineArticle10.1016/j.toxlet.2013.06.213