Verrucarin A enhances TRAIL-induced apoptosis via NF-κB-mediated Fas overexpression

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Title
Verrucarin A enhances TRAIL-induced apoptosis via NF-κB-mediated Fas overexpression
Author(s)
R G P T Jayasooriya; D O Moon; S G Yun; Y H Choi; Y Asami; Mun-Ock KimJae-Hyuk JangBo Yeon KimJong Seog Ahn; G Y Kim
Bibliographic Citation
Food and Chemical Toxicology, vol. 55, no. 1, pp. 1-7
Publication Year
2013
Abstract
We investigated whether verrucarin A (VA) sensitizes HepG2 hepatoma cells to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. We found that VA alone induces little apoptosis, but when combined with TRAIL (VA/TRAIL), it triggered significant apoptosis, causing little or no toxicity in normal mouse splenocytes. VA/TRAIL-induced cell death is involved in the loss of mitochondrial transmembrane potential and the consequent activation of caspases. Because nuclear factor (NF)-κB inhibition has been known as a critical target in TRAIL-mediated apoptosis, we also investigated the role of NF-κB in VA/TRAIL treatment. We found that VA upregulated the DNA binding activity of NF-κB, but that the antioxidants glutathione and N-acetyl-. l-cysteine, as well as NF-κB inhibitor MG132, and mutant-IκB (m-IκB) transfection, significantly downregulated VA/TRAIL-induced cell death by inhibiting caspase-3 and NF-κB activities. Transfection of mutant-eIF2α also resulted in a decrease in VA/TRAIL-induced cell death by inhibiting of caspase-3, but not NF-κB activity. Although VA/TRAIL treatment led to an increase of DR5 expression, transfection of m-IκB had no influence on the DR5 expressional level. Finally, we showed that NF-κB-mediated Fas expression is critical to VA/TRAIL-induced apoptosis. Taken together, these results indicate that VA/TRAIL sensitizes HepG2 cells to apoptosis via NF-κB-mediated overexpression of Fas
Keyword
FasNF-κBTumor necrosis factor-related apoptosis inducing ligandVerrucarin A
ISSN
0278-6915
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.fct.2012.12.045
Type
Article
Appears in Collections:
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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