Abstract | BACKGROUND: METHODS: The cytotoxic and apoptotic effects of indoximod alone or IFN-γ or TNF-α induction to mimic an inflammatory environment were evaluated by WST-1, Annexin V, cell cycle analysis, and acridine orange (AO)/ ethidium bromide (EtBr) staining. Furthermore, the expression levels of IDO1 and PD-L1 expression were analyzed by RT-PCR. RESULTS: Our results demonstrated that indoximod significantly decreased the TNBC cell viability through apoptotic cell death (p < .05). The combination of indoximod and TNF-α was more effective than indoximod and IFN-γ stimulation or indoximod alone in TNBC cells. Additionally, PD-L1 expression level was significantly up-regulated after treatment with indoximod and TNF-α or IFN-γ combinations (p < .05). CONCLUSIONS:
Indoximod exhibited a therapeutic potential in TNBC cells and pro-inflammatory cytokines could affect the effectiveness of indoximod. However, further studies are required to identify the role of the IDO-associated signaling pathways, the molecular mechanisms of indoximod induced apoptotic cell death, and the relationship between IDO inhibition by IDO inhibitors and pro-inflammatory cytokine levels.
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Authors | Gamze Guney Eskiler, Cemil Bilir |
Journal | Immunopharmacology and immunotoxicology
(Immunopharmacol Immunotoxicol)
Vol. 43
Issue 5
Pg. 554-561
(Oct 2021)
ISSN: 1532-2513 [Electronic] England |
PMID | 34314307
(Publication Type: Journal Article)
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Chemical References |
- B7-H1 Antigen
- CD274 protein, human
- Cytokines
- Inflammation Mediators
- Tumor Necrosis Factor-alpha
- Interferon-gamma
- Tryptophan
- 1-methyltryptophan
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Topics |
- B7-H1 Antigen
(biosynthesis)
- Cell Line, Tumor
- Cell Survival
(drug effects, physiology)
- Cytokines
(administration & dosage)
- Dose-Response Relationship, Drug
- Humans
- Inflammation Mediators
(administration & dosage)
- Interferon-gamma
(administration & dosage)
- Treatment Outcome
- Triple Negative Breast Neoplasms
(drug therapy, metabolism)
- Tryptophan
(administration & dosage, analogs & derivatives)
- Tumor Necrosis Factor-alpha
(administration & dosage)
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