論文 - 詳細
| RRC ID | 10935 |
|---|---|
| 著者 | Kobori M, Yoshida M, Ohnishi-Kameyama M, Shinmoto H. |
| タイトル | Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells. |
| ジャーナル | Br J Pharmacol |
| Abstract |
BACKGROUND AND PURPOSE:5alpha,8alpha-Epidioxy-22E-ergosta-6, 22-dien-3beta-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol peroxide. EXPERIMENTAL APPROACH:After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS-induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT-PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells. KEY RESULTS:Ergosterol peroxide suppressed LPS-induced TNF-alpha secretion and IL-1alpha/beta expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS-induced DNA binding activity of NF-kappaB and C/EBPbeta, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down-regulated the expression of low-density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG-CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress-inducible genes, and the cyclin-dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon-inducible genes. CONCLUSION AND IMPLICATION:Our results suggest that ergosterol peroxide and ergosterol suppress LPS-induced inflammatory responses through inhibition of NF-kappaB and C/EBPbeta transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells. |
| 巻・号 | 150(2) |
| ページ | 209-19 |
| 公開日 | 2007-1-1 |
| DOI | 10.1038/sj.bjp.0706972 |
| PII | 0706972 |
| PMID | 17160010 |
| PMC | PMC2042906 |
| MeSH | Adenocarcinoma Agaricales / chemistry* Animals Anti-Inflammatory Agents / pharmacology* Antineoplastic Agents / pharmacology* Cell Line Cell Proliferation / drug effects Chemoprevention Colonic Neoplasms Ergosterol / analogs & derivatives* Ergosterol / pharmacology Gene Expression / drug effects HT29 Cells Humans Inflammation / metabolism Lipopolysaccharides / pharmacology Macrophages / drug effects* Macrophages / metabolism Oxidation-Reduction Reverse Transcriptase Polymerase Chain Reaction |
| IF | 7.73 |
| 引用数 | 116 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) WI-38(RCB0702) |