A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells

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dc.contributor.authorAtmaca H.
dc.contributor.authorBozkurt E.
dc.contributor.authorUzunoglu S.
dc.contributor.authorUslu R.
dc.contributor.authorKaraca B.
dc.date.accessioned2024-07-22T08:18:05Z
dc.date.available2024-07-22T08:18:05Z
dc.date.issued2013
dc.description.abstractTrabectedin (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.
dc.identifier.DOI-ID10.1016/j.toxlet.2013.06.213
dc.identifier.issn03784274
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/17180
dc.language.isoEnglish
dc.publisherElsevier Ireland Ltd
dc.subjectApoptosis
dc.subjectbcl-2-Associated X Protein
dc.subjectbcl-Associated Death Protein
dc.subjectBreast Neoplasms
dc.subjectCaspase 3
dc.subjectCaspase 7
dc.subjectCell Line, Tumor
dc.subjectCytochromes c
dc.subjectDioxoles
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectMCF-7 Cells
dc.subjectMitochondria
dc.subjectMitochondrial Proteins
dc.subjectReactive Oxygen Species
dc.subjectReceptors, TNF-Related Apoptosis-Inducing Ligand
dc.subjectTetrahydroisoquinolines
dc.subjectcaspase 3
dc.subjectcytochrome c
dc.subjectdeath receptor
dc.subjectepidermal growth factor receptor 2
dc.subjectestrogen receptor
dc.subjectprotein Bax
dc.subjectprotein bcl xl
dc.subjectreactive oxygen metabolite
dc.subjecttrabectedin
dc.subjecttumor necrosis factor related apoptosis inducing ligand
dc.subject1,3 dioxolane derivative
dc.subjectBAD protein, human
dc.subjectBAX protein, human
dc.subjectCASP3 protein, human
dc.subjectCASP7 protein, human
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectcytochrome c
dc.subjectDIABLO protein, human
dc.subjectmitochondrial protein
dc.subjectprotein BAD
dc.subjectprotein Bax
dc.subjectreactive oxygen metabolite
dc.subjectsignal peptide
dc.subjecttetrahydroisoquinoline derivative
dc.subjectTNFRSF10A protein, human
dc.subjecttrabectedin
dc.subjecttumor necrosis factor related apoptosis inducing ligand receptor
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectarticle
dc.subjectbreast cancer
dc.subjectcell strain MCF 7
dc.subjectconcentration (parameters)
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectEcteinascidia turbinata
dc.subjectenzyme metabolism
dc.subjectgenotype
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmitochondrion
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein folding
dc.subjectUrochordata
dc.subjectapoptosis
dc.subjectbreast tumor
dc.subjectdrug effects
dc.subjectfemale
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectMCF 7 cell line
dc.subjectmetabolism
dc.subjectpathology
dc.subjecttumor cell line
dc.titleA diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells
dc.typeArticle

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