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- NF-κB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells
- Osong Kwon; Kyong A Kim; Sun Ok Kim; Ryong Ha; Won Keun Oh; Min-Soo Kim; Hee-Sik Kim; G D Kim; J W Kim; M Jung; C H Kim; Jong Seog Ahn; Bo Yeon Kim
- Bibliographic Citation
- Carcinogenesis, vol. 27, no. 11, pp. 2258-2268
- Publication Year
- 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.
- Oxford Univ Press
- Appears in Collections:
- Jeonbuk Branch Institute > Microbial Biotechnology Research Center > 1. Journal Articles
Synthetic Biology and Bioengineering Research Institute > Cell Factory Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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