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: Misato Shimura, Masafumi Yamamoto, Gen Fujii, Mami Takahashi, Masami Komiya, Nobuharu Noma, Sei-ichi Tanuma, Akinori Yanaka, Michihiro Mutoh
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 12 Pg. 2186-91 ( 2012) ISSN: 1347-5215 [Electronic] Japan
• PMID: 23018603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2,6-diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione
• Anti-Inflammatory Agents
• I-kappa B Proteins
• Inflammation Mediators
• Interleukin-6
• Isoindoles
• NF-kappa B
• Oxazoles
• RNA, Messenger
• SK-1009

Topics

• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, metabolism)
• Humans
• I-kappa B Proteins (metabolism)
• Inflammation (drug therapy, metabolism)
• Inflammation Mediators (metabolism)
• Interleukin-6 (genetics, metabolism)
• Isoindoles (pharmacology)
• Macrophages (drug effects, metabolism)
• NF-kappa B (antagonists & inhibitors)
• Oxazoles (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Signal Transduction