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An IκB kinase 2 inhibitor IMD-0354 suppresses the survival of adult T-cell leukemia cells

Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Cancer Science (Impact Factor: 3.53). 09/2011; 103(1):100-6. DOI: 10.1111/j.1349-7006.2011.02110.x
Source: PubMed

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.

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    • "IMD-0354, an inhibitor of the NF-κB pathway, was initially designed to inhibit inflammation [48,49], but recently proven to have anticancer properties [16,50,51]. Here, we wanted to assess if IMD-0354 also affects CSCs, as indicated by prior screening. "
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