title: Novel compound SK-1009 suppresses interleukin-6 expression through modulation of activation of nuclear factor-kappaB pathway.
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.
authors.affiliation: Division of Cancer Prevention Research, National Cancer Center Research Institute, 5–1–1 Tsukiji, Chuo-ku, Tokyo 104–0045, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Shimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Gen
authors.initials: G
authors.lastname: Fujii
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masami
authors.initials: M
authors.lastname: Komiya
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Noma
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
authors.forename: Akinori
authors.initials: A
authors.lastname: Yanaka
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D054833:Isoindoles / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C501339:2-(2,6-diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione; D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D054833:Isoindoles; D016328:NF-kappa B; D010080:Oxazoles; D012333:RNA, Messenger; C581103:SK-1009