Please use this identifier to cite or link to this item: https://ir.swu.ac.th/jspui/handle/123456789/13455
ชื่อเรื่อง: Suppression of Nrf2 confers chemosensitizing effect through enhanced oxidant-mediated mitochondrial dysfunction
ผู้แต่ง: Sompakdee V.
Prawan A.
Senggunprai L.
Kukongviriyapan U.
Samathiwat P.
Wandee J.
Kukongviriyapan V.
Keywords: acetylcysteine
cisplatin
cyclosporine
dichlorodihydrofluorescein diacetate
fluorescent dye
luteolin
reactive oxygen metabolite
small interfering RNA
sulforhodamine B
tempol
transcription factor Nrf2
[5,10,15,20 tetrakis(4 carboxyphenyl) 21h,23h porphine]manganese(iii) chloride
antineoplastic agent
cisplatin
NFE2L2 protein, human
oxidizing agent
transcription factor Nrf2
Article
bile duct carcinoma
cell death
chemosensitization
controlled study
cytotoxicity
disorders of mitochondrial functions
drug cytotoxicity
drug mechanism
human
human cell
human tissue
KKU-100 cell line
mitochondrial membrane potential
oxidative stress
priority journal
protein expression
reverse transcription polymerase chain reaction
antagonists and inhibitors
drug effect
gene knockdown
metabolism
mitochondrion
physiology
procedures
tumor cell line
Antineoplastic Agents
Cell Line, Tumor
Cisplatin
Gene Knockdown Techniques
Humans
Membrane Potential, Mitochondrial
Mitochondria
NF-E2-Related Factor 2
Oxidants
Reactive Oxygen Species
วันที่เผยแพร่: 2018
บทคัดย่อ: Aims: Transcription factor Nrf2, which regulates the expression of cytoprotective and antioxidant enzymes, contributes to proliferation and resistance to chemotherapy in cancer. The inhibition of Nrf2 can sensitize cholangiocarcinoma (CCA) cells to the cytotoxicity of several chemotherapeutic agents. In this study, we investigated the mechanism of this chemosensitizing effect. Main methods: KKU-100 cells were used in the study. Nrf2 expression was knocked down by siRNA and expression was validated by reverse transcription and polymerase chain reaction. Cytotoxicity was assessed by sulforhodamine B method. Intracellular reactive oxygen species (ROS) was examined by fluorescent dye, dichlorofluorescin diacetate method and mitochondrial transmembrane potential was assessed by JC1 dye assay. Key findings: Cytotoxicity of cisplatin (Cis) in KKU-100 cells was enhanced by knockdown of Nrf2 expression. The enhanced cytotoxic effect was abolished by treatment with N-acetylcysteine, TEMPOL and MnTBAP. Cells with Nrf2 knockdown or Cis treatment increased production of ROS, and ROS was markedly enhanced by a combination of Nrf2 knockdown and Cis. The increased ROS formation was associated with a decrease in mitochondrial transmembrane potential (Δψm), where this decrease was prevented by antioxidant compounds. The loss of Δψm and cell death were prevented by cyclosporine, an inhibitor of mitochondrial permeability transition pore (MPTP). Luteolin inhibited Nrf2 and markedly enhanced cytotoxicity in combination with Cis. Significance: Inhibition of Nrf2 is a feasible strategy in enhancing antitumor activity of chemotherapeutic agents and improving efficacy of chemotherapy in CCA. © 2018 Elsevier Masson SAS
URI: https://ir.swu.ac.th/jspui/handle/123456789/13455
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042862855&doi=10.1016%2fj.biopha.2018.02.112&partnerID=40&md5=46efb9ce6322ce12f1fa4935518a2558
ISSN: 7533322
Appears in Collections:Scopus 1983-2021

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