| Autor: |
Quach HT; Department of Applied Biology, Kyoto Institute of Technology., Kondo T; Department of Applied Biology, Kyoto Institute of Technology., Watanabe M; Department of Applied Biology, Kyoto Institute of Technology., Tamura R; Department of Applied Biology, Kyoto Institute of Technology., Yajima Y; Department of Applied Biology, Kyoto Institute of Technology., Sayama S; Department of Natural Sciences (Chemistry), Fukushima Medical University., Ando M; Department of Chemistry and Chemical Engineering, Niigata University., Kataoka T; Department of Applied Biology, Kyoto Institute of Technology.; The Center for Advanced Insect Research Promotion (CAIRP), Kyoto Institute of Technology. |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2017; Vol. 40 (10), pp. 1669-1677. |
| DOI: |
10.1248/bpb.b17-00170 |
| Abstrakt: |
The transcription factor nuclear factor κB (NF-κB) regulates various biological processes, including inflammatory responses. We previously reported that eudesmane-type sesquiterpene lactones inhibited multiple steps in the canonical NF-κB signaling pathway induced by tumor necrosis factor-α and interleukin-1α. In contrast, the biological activities of eudesmane-type sesquiterpene lactones on the non-canonical NF-κB signaling pathway remain unclear. In the present study, we found that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), inhibited NF-κB luciferase reporter activity induced by lymphotoxin β (LTβ) in human lung carcinoma A549 cells. Although SRC2 did not prevent the processing of the NF-κB subunit p100 induced by LTβ, it inhibited the nuclear translocation of RelB and p52 in response to the LTβ stimulation. In contrast to (-)-dehydroxymethylepoxyquinomicin, SRC2 inhibited the LTβ-induced nuclear translocation of the RelB (C144S) mutant in a manner similar to wild-type RelB. While eudesmane derivatives possessing an α-bromoketone moiety or α,β-unsaturated carbonyl moieties inhibited LTβ-induced NF-κB luciferase reporter activity, eudesmane derivatives possessing an α-bromoketone moiety exhibited stronger inhibitory activity on the LTβ-induced nuclear translocation of RelB than those possessing a single α-methylene-γ-lactone moiety. The results of the present study revealed that SRC2 inhibits the nuclear translocation of RelB in the non-canonical NF-κB signaling pathway induced by LTβ. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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