2-(2-6-diisopropylphenyl)-5-hydroxy-1h-isoindole-1-3-dione and Colonic-Neoplasms

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.

Topics: Anti-Inflammatory Agents; Cell Line, Tumor; Colonic Neoplasms; Humans; I-kappa B Proteins; Inflammation; Inflammation Mediators; Interleukin-6; Isoindoles; Macrophages; NF-kappa B; Oxazoles; RNA, Messenger; Signal Transduction