PMID- 34314307
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20220426
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 43
IP  - 5
DP  - 2021 Oct
TI  - The efficacy of indoximod upon stimulation with pro-inflammatory cytokines in 
      triple-negative breast cancer cells.
PG  - 554-561
LID - 10.1080/08923973.2021.1953064 [doi]
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) inhibition has received much 
      attention in cancer immunotherapy due to its role in immune escape in cancer 
      cells. Additionally, changes in the pro-inflammatory cytokine levels can affect 
      tumor growth and metastasis as well as the effectiveness of immunotherapy. The 
      purpose of this study was for the first time to determine the effects of 
      indoximod as an IDO inhibitor on triple-negative breast cancer (TNBC) and to 
      assess the link between the efficacy of indoximod and IFN-gamma or TNF-alpha stimulation. 
      METHODS: The cytotoxic and apoptotic effects of indoximod alone or IFN-gamma or TNF-alpha 
      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-alpha was more effective than 
      indoximod and IFN-gamma stimulation or indoximod alone in TNBC cells. Additionally, 
      PD-L1 expression level was significantly up-regulated after treatment with 
      indoximod and TNF-alpha or IFN-gamma 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.
FAU - Guney Eskiler, Gamze
AU  - Guney Eskiler G
AUID- ORCID: 0000-0002-2088-9914
AD  - Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, 
      Turkey.
FAU - Bilir, Cemil
AU  - Bilir C
AD  - Department of Medical Oncology, Faculty of Medicine, Istinye University VMMedical 
      Park Pendik Hospital, Istanbul, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20210727
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 8DUH1N11BX (Tryptophan)
RN  - XD0FY1J13B (1-methyltryptophan)
SB  - IM
MH  - B7-H1 Antigen/biosynthesis
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/physiology
MH  - Cytokines/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Inflammation Mediators/*administration & dosage
MH  - Interferon-gamma/administration & dosage
MH  - Treatment Outcome
MH  - Triple Negative Breast Neoplasms/drug therapy/*metabolism
MH  - Tryptophan/administration & dosage/*analogs & derivatives
MH  - Tumor Necrosis Factor-alpha/administration & dosage
OTO - NOTNLM
OT  - Triple-negative breast cancer
OT  - indoleamine 2,3-dioxygenase (IDO)
OT  - indoximod
OT  - pro-inflammatory cytokines
EDAT- 2021/07/28 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/07/27 17:14
PHST- 2021/07/28 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/07/27 17:14 [entrez]
AID - 10.1080/08923973.2021.1953064 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2021 Oct;43(5):554-561. doi: 
      10.1080/08923973.2021.1953064. Epub 2021 Jul 27.