NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation

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Title
NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation
Author(s)
Bo Yeon Kim; Kyung A Kim; OSong Kwon; Sun Ok Kim; Min-Soo Kim; Beom Seok Kim; Won Keun Oh; G D Kim; M Jung; Jong Seog Ahn
Bibliographic Citation
Carcinogenesis, vol. 26, no. 8, pp. 1395-1403
Publication Year
2005
Abstract
Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-κB) but not of either Akt or MAPK kinase (MEK), increased the radiosensitization of Ki-Ras transformed human prostate epithelial 267B1/K-ras cells. Proteosome inhibitor-1 (Pro1) reduced NF-κB activation, and this inhibition was accompanied by increased levels of cytoplasmic IκBα and p65/RelA. However, translocation of p50/ NF-κB1 did not occur on exposure to IR, suggesting the cell-specific involvement of p50 in radiation signaling. Clonogenic cell survival and soft agar assays further confirmed the increased radiosensitivity of 267B1/K-ras cells by proteosome inhibition. In addition, proteosome inhibition enhanced the IR-induced degradation of apoptotic protein caspases 8 and 3, with the level of antiapoptotic protein Bcl-2 being unaffected, suggesting the involvement of an apoptotic process in IR-induced cell death of 267B1/K-ras cells. LY294002 and PD98059, specific inhibitors of phosphatidylinositol-3-kinase (PI3K) and MEK, respectively however, did not affect the radiosensitization. All these results suggest an application of blocking NF-κB activation pathway to the development of anticancer therapeutics in IR-induced radiotherapy of Ki-Ras-transformed cancer cells.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgi081
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Microbial Biotechnology Research Center > 1. Journal Articles
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