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Title 

NF-κB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells

Authors 

Osong KwonKyong A KimSun Ok KimRyong HaWon Keun OhMin-Soo KimHee-Sik KimG D KimJ W KimM JungC H KimJong Seog AhnBo Yeon Kim

Publisher 

Oxford University Press (OUP)

Issue Date 

2006

Citation 

Carcinogenesis, vol. 27, no. 11, pp. 2258-2268

Keywords 

2 (2 amino 3 methoxyphenyl)chromonecaspase 3caspase 8I kappa BI kappa B kinase alphaI kappa B kinase betaimmunoglobulin enhancer binding proteinimmunoglobulin enhancer binding protein 1K ras proteinmitogen activated protein kinase

Abstract 

Chemoresistance has been one of the major problems in anticancer therapy. In our effort to find a potential molecular target for overcoming the chemoresistance in prostate cancer, a promising anticancer drug trichostatin A (TSA) induced cell death was found to be compromised by enhanced NF-κB activation in 267B1/K-ras human prostate epithelial cancer cells. However, both the NF-κB activation and chemoresistance were reduced by pretreatment with proteasome inhibitor-I (ProI), accompanied by accumulations of both IκBα and p65/RelA (but not p50/NF-κB1) in the cytoplasm. Clonogenic cell survival and soft agar assays further confirmed the increased TSA chemosensitivity of 267B1/K-ras cells by ProI treatment. Moreover, dominant negative mutant of IKKβ, IκBα and p65 enhanced the chemosensitization, too. Unexpectedly, using LY294002 and PD98059, phosphatidylinositol-3-kinase and mitogen-activated protein kinase were also implied in TSA chemoresistance through NF-κB activation, while these compounds had showed no effect on radiosensitization in the cells. On the other hand, together with TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, activations of caspase-8 and caspase-3 by TSA and ProI were noticed, suggesting the involvement of apoptotic process in chemosensitization of 267B1/K-ras cells. Altogether, these results suggest that blocking the NF-κB activation pathway could be an efficient target for improving the TSA chemosensitization and applying to the development of anticancer therapeutics in Ki-Ras-overexpressing tumorigenic cells, including prostate cancer.

ISSN 

0143-3334

Link 

http://dx.doi.org/10.1093/carcin/bgl097

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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