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김은희

Kim, Eunhee
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Monensin, a polyether ionophore antibiotic, overcomes TRAIL resistance in glioma cells via endoplasmic reticulum stress, DR5 upregulation and c-FLIP downregulation

Author(s)
Yoon, Mi JinKang, You JungKim, In YoungKim, Eun HeeLee, Ju AhnLim, Jun HeeKwon, Taeg KyuChoi, Kyeong Sook
Issued Date
2013-08
DOI
10.1093/carcin/bgt137
URI
https://scholarworks.unist.ac.kr/handle/201301/20169
Fulltext
http://carcin.oxfordjournals.org/content/34/8/1918
Citation
CARCINOGENESIS, v.34, no.8, pp.1918 - 1928
Abstract
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is preferentially cytotoxic to cancer cells over normal cells. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL. Monensin (a polyether ionophore antibiotic that is widely used in veterinary medicine) and salinomycin (a compound that is structurally related to monensin and shows cancer stem cell-inhibiting activity) are currently recognized as anticancer drug candidates. In this study, we show that monensin effectively sensitizes various glioma cells, but not normal astrocytes, to TRAIL-mediated apoptosis; this occurs at least partly via monensin-induced endoplasmic reticulum (ER) stress, CHOP-mediated DR5 upregulation and proteasome-mediated downregulation of c-FLIP. Interestingly, other polyether antibiotics, such as salinomycin, nigericin, narasin and lasalocid A, also stimulated TRAIL-mediated apoptosis in glioma cells via ER stress, CHOP-mediated DR5 upregulation and c-FLIP downregulation. Taken together, these results suggest that combined treatment of glioma cells with TRAIL and polyether ionophore antibiotics may offer an effective therapeutic strategy
Publisher
OXFORD UNIV PRESS
ISSN
0143-3334
Keyword
VALENT CARBOXYLIC IONOPHORESINDUCED APOPTOSISPROTEIN-DEGRADATIONPROSTATE-CANCERRAT HEPATOCYTESCELLULAR FLIPSALINOMYCINDEATHGROWTHINHIBITION

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