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Title: An IκB kinase 2 inhibitor IMD-0354 suppresses the survival of adult T-cell leukemia cells
Authors: Uota, S.
Zahidunnabi Dewan, M.
Saitoh, Y.
Muto, S.
Itai, A.
Utsunomiya, A.
Watanabe, T.
Yamamoto, N. 
Yamaoka, S.
Issue Date: Jan-2012
Citation: Uota, S., Zahidunnabi Dewan, M., Saitoh, Y., Muto, S., Itai, A., Utsunomiya, A., Watanabe, T., Yamamoto, N., Yamaoka, S. (2012-01). An IκB kinase 2 inhibitor IMD-0354 suppresses the survival of adult T-cell leukemia cells. Cancer Science 103 (1) : 100-106. ScholarBank@NUS Repository.
Abstract: Adult T-cell leukemia (ATL) is a fatal T-cell malignancy associated with human T-cell leukemia virus type I infection. The aberrant expression of nuclear factor-κB (NF-κB) is considered to contribute to the malignant phenotype and chemo-resistance of ATL cells. Because of the poor prognosis of ATL, the development of new therapeutic strategies is direly needed. In the present study, we show that an IκB kinase 2 (IKK2) inhibitor, IMD-0354, efficiently inhibits the survival of CD4 +CD25 + primary ATL cells and prevents the growth of or induces apoptosis of patient-derived ATL cell lines. Assays of transcription with integrated forms of reporter genes revealed that IMD-0354 suppresses NF-κB-dependent transcriptional activity. Moreover, the daily administration of IMD-0354 prevents the growth of tumors in mice inoculated with ATL cells. Our results suggest that targeting IKK2 with a small molecule inhibitor, such as IMD-0354, is an attractive strategy for the treatment of ATL. © 2011 Japanese Cancer Association.
Source Title: Cancer Science
ISSN: 13479032
DOI: 10.1111/j.1349-7006.2011.02110.x
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