Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Novel Compound SK-1009 Suppresses Interleukin-6 Expression through Modulation of Activation of Nuclear Factor-KappaB Pathway
Misato ShimuraMasafumi YamamotoGen FujiiMami TakahashiMasami KomiyaNobuharu NomaSei-ichi TanumaAkinori YanakaMichihiro Mutoh
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2012 Volume 35 Issue 12 Pages 2186-2191

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Abstract

Although interleukin-6 (IL-6) is an important biological mediator playing an indispensable role in inflammation and cancer, few inhibitors and suppressors are known. In the present study, the underlying mechanisms of a novel chemically synthesized compound SK-1009, which has suppressive properties on IL-6 production in human macrophage cells, were examined. SK-1009 suppressed IL-6 mRNA levels in human colon cancer cells. Thus, the influence of SK-1009 on transcription factor, nuclear factor-kappaB (NF-κB), which is involved in expression of the IL-6 gene was assessed. SK-1009 was found to suppress degradation of I-κB, an NF-κB inhibitory factor, and consequently inhibited the NF-κB activation pathway. The inhibitory property was almost the same as other NF-κB inhibitors, such as 5HPP-33. Thus, SK-1009 exerts a potent inhibitory effect on IL-6 expression, apparently mediated by modulation of activation of NF-κB transcription factor.

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© 2012 The Pharmaceutical Society of Japan
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