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The novel NF-kappa ...
The novel NF-kappa B inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia
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- Kanduri, Meena (författare)
- Uppsala universitet,Hematologi och immunologi
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Tobin, Gerard (författare)
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- Åleskog, Anna (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Nilsson, Kenneth (författare)
- Uppsala universitet,Hematologi och immunologi
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- Rosenquist, Richard (författare)
- Uppsala universitet,Hematologi och immunologi
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visa färre...
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(creator_code:org_t)
- 2011-03-25
- 2011
- Engelska.
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 1, s. e12-
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Nuclear factor-kappa B (NF-kappa B) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-kappa B inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of I kappa B alpha by IkB kinases, thus preventing NF-kappa B release. In this study, we investigated if IMD-0354 can inhibit NF-kappa B activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-kappa B were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8-48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-kappa B in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo.
Nyckelord
- chronic lymphocytic leukemia
- IMD-0354
- nuclear factor-kappa B
- apoptosis
- drug sensitivity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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