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

Bo Yeon Kim, Osong Kwon, Sun Ok Kim, Min Soo Kim, Beom Seok Kim, Won Keun Oh, Gun Do Kim, Mira Jung, Jong Seog Ahn

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1395-1403
Number of pages9
JournalCarcinogenesis
Volume26
Issue number8
DOIs
Publication statusPublished - 2005 Aug 1
Externally publishedYes

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Ionizing Radiation
Mitogen-Activated Protein Kinase Kinases
Cell Death
Phosphatidylinositol 3-Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Caspase 8
NF-kappa B
Radiation Tolerance
Caspase 3
Proteolysis
Agar
Prostate
Neoplasms
Cell Survival
Transcription Factors
Radiotherapy
Radiation
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

Kim, B. Y., Kwon, O., Kim, S. O., Kim, M. S., Kim, B. S., Oh, W. K., ... Ahn, J. S. (2005). NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation. Carcinogenesis, 26(8), 1395-1403. https://doi.org/10.1093/carcin/bgi081

NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation. / Kim, Bo Yeon; Kwon, Osong; Kim, Sun Ok; Kim, Min Soo; Kim, Beom Seok; Oh, Won Keun; Kim, Gun Do; Jung, Mira; Ahn, Jong Seog.

In: Carcinogenesis, Vol. 26, No. 8, 01.08.2005, p. 1395-1403.

Research output: Contribution to journalArticle

Kim, BY, Kwon, O, Kim, SO, Kim, MS, Kim, BS, Oh, WK, Kim, GD, Jung, M & Ahn, JS 2005, 'NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation', Carcinogenesis, vol. 26, no. 8, pp. 1395-1403. https://doi.org/10.1093/carcin/bgi081
Kim, Bo Yeon ; Kwon, Osong ; Kim, Sun Ok ; Kim, Min Soo ; Kim, Beom Seok ; Oh, Won Keun ; Kim, Gun Do ; Jung, Mira ; Ahn, Jong Seog. / NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation. In: Carcinogenesis. 2005 ; Vol. 26, No. 8. pp. 1395-1403.
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