ArticleWorld journal of gastroenterology2010
Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells.
Article in World journal of gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Brusatol enhances the chemotherapy efficacy of Cisplatin and Gemcitabine in KKU-100 cholangiocarcinoma cells through ROS-mediated apoptosis.Scientific reports · 2026Article
- Ameliorating Paraquat-induced Nephrotoxicity in Rats: Protective Effects of Nanocurcumin on Renal Histology and Molecular Pathways.Pharmaceutical nanotechnology · 2026Article
- DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells.Redox biology · 2024Article
- Dicoumarol: from chemistry to antitumor benefits.Chinese medicine · 2022Review
- Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines.The American journal of pathology · 2022Review
- Copy number profiling of circulating free DNA predicts transarterial chemoembolization response in advanced hepatocellular carcinoma.Molecular oncology · 2022Article
- Derrischalcone suppresses cholangiocarcinoma cells through targeting ROS-mediated mitochondrial cell death, Akt/mTOR, and FAK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- NAD(P)H:quinone oxidoreductase 1 determines radiosensitivity of triple negative breast cancer cells and is controlled by long non-coding RNA NEAT1.International journal of medical sciences · 2020Article
- Pharmacogenetics of hepatocellular carcinoma and cholangiocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Effect of β-Eudesmol on NQO1 suppression-enhanced sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.BMC pharmacology & toxicology · 2018Article
- Suppression of glutathione S-transferases potentiates the cytotoxic effect of phenethyl isothiocyanate in cholangiocarcinoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Azoreductases in drug metabolism.British journal of pharmacology · 2017Review
- Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells.Oncology letters · 2017Article
- Clinicopathological implications of NQO1 overexpression in the prognosis of pancreatic adenocarcinoma.Oncology letters · 2017Article
- Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells.PloS one · 2017Article
- Nrf2 inhibition sensitizes cholangiocarcinoma cells to cytotoxic and antiproliferative activities of chemotherapeutic agents.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Haem oxygenase 1 expression is associated with prognosis in cholangiocarcinoma patients and with drug sensitivity in xenografted mice.Cell proliferation · 2016Article
- Repression of Nrf2 enhances antitumor effect of 5-fluorouracil and gemcitabine on cholangiocarcinoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Article
- Thiopurines induce oxidative stress in T-lymphocytes: a proteomic approach.Mediators of inflammation · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate whether dicoumarol, a potent inhibitor of NAD(P)H quinone oxidoreductase-1 (NQO1), potentiates gemcitabine to induce cytotoxicity in cholangiocarcinoma cells (CCA) and the role of reactive oxygen generation in sensitizing the cells.
methodsFour human cell lines with different NQO1 activity were used; the human CCA cell lines, KKU-100, KKU-OCA17, KKU-M214, and Chang liver cells. NQO1 activity and mRNA expression were determined. The cells were pretreated with dicoumarol at relevant concentrations before treatment with gemcitabine. Cytotoxicity was determined by staining with fluorescent dyes. Oxidant formation was examined by assay of cellular glutathione levels and reactive oxygen species production by using dihydrofluorescein diacetate. Measurement of mitochondrial transmembrane potential was performed by using JC-1 fluorescent probe. Western blotting analysis was performed to determine levels of survival related proteins.
resultsDicoumarol markedly enhanced the cytotoxicity of gemcitabine in KKU-100 and KKU-OCA17, the high NQO1 activity and mRNA expressing cells, but not in the other cells with low NQO1 activity. Dicoumarol induced a marked decrease in cellular redox of glutathione in KKU-100 cells, in contrast to KKU-M214 cells. Dicoumarol at concentrations that inhibited NQO1 activity did not alter mitochondrial transmembrane potential and production of reactive oxygen species. Gemcitabine alone induced activation of NF-kappaB and Bcl-(XL) protein expression. However, gemcitabine and dicoumarol combination induced increased p53 and decreased Bcl-(XL) levels in KKU-100, but not in KKU-M214 cells.
conclusionNQO1 may be important in sensitizing cells to anticancer drugs and inhibition of NQO1 may be a strategy for the treatment of CCA.
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