The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor ? stimulation

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dc.contributor.authorBilir, C.
dc.contributor.authorEskiler, G.G.
dc.contributor.authorBilir, F.
dc.date.accessioned2024-05-19T14:33:14Z
dc.date.available2024-05-19T14:33:14Z
dc.date.issued2023
dc.departmentİstinye Üniversitesien_US
dc.description.abstractContext: Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. Aims: In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-? (TNF-?) stimulation. Materials and Methods: The anticancer activity of EPA and L-1MT alone and in combination with TNF-? was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. Statistical Analysis Used: SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. Results: EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-? alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-? suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-? stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Conclusions: Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations. © 2022 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.en_US
dc.identifier.doi10.4103/jcrt.jcrt_2365_21
dc.identifier.endpage80en_US
dc.identifier.issn0973-1482
dc.identifier.issue8en_US
dc.identifier.pmid37147986en_US
dc.identifier.scopus2-s2.0-85159113341en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage74en_US
dc.identifier.urihttps://doi.org/10.4103/jcrt.jcrt_2365_21
dc.identifier.urihttps://hdl.handle.net/20.500.12713/4151
dc.identifier.volume19en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Medknow Publicationsen_US
dc.relation.ispartofJournal of Cancer Research and Therapeuticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240519_kaen_US
dc.subject3-Dioxygenaseen_US
dc.subject3-Dioxygenase İnhibitorsen_US
dc.subjectEpacadostaten_US
dc.subjectİndoleamine 2en_US
dc.subjectİndoleamine 2en_US
dc.subjectTriple-Negative Breast Canceren_US
dc.subjectTumor Necrosis Factor-?en_US
dc.titleThe cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor ? stimulationen_US
dc.typeArticleen_US

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