Home LiteratureArticle Details
PMID: 17160010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells.

British journal of pharmacology ·Vol. 150 ·No. 2 ·2007-01-00 ·Pages 209-19

Kobori M, Yoshida M, Ohnishi-Kameyama M, Shinmoto H

Abstract

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. 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. 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. 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.

MeSH Terms
Adenocarcinoma Agaricales/chemistry Animals Anti-Inflammatory Agents/pharmacology Antineoplastic Agents/pharmacology Cell Line Cell Proliferation/drug effects Chemoprevention Colonic Neoplasms Ergosterol/analogs & derivatives,pharmacology Gene Expression/drug effects HT29 Cells Humans Inflammation/metabolism Lipopolysaccharides/pharmacology Macrophages/drug effects,metabolism Oxidation-Reduction Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Anti-Inflammatory Agents Antineoplastic Agents Lipopolysaccharides ergosterol-5,8-peroxide Ergosterol
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kobori M
National Food Research Institute, Tsukuba, Ibaraki, Japan. kobori@affrc.go.jp
Yoshida M
Ohnishi-Kameyama M
Shinmoto H
References (42)
42 references, click to expand
  1. DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1.
    Carcinogenesis. 2004 Jul;25(7):1293-8 PMID: 14976132
  2. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation.
    Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G7-17 PMID: 15194558
  3. Disruption of cholesterol homeostasis by plant sterols.
    J Clin Invest. 2004 Sep;114(6):813-22 PMID: 15372105
  4. cDNA structures and regulation of two interferon-induced human Mx proteins.
    Mol Cell Biol. 1989 Nov;9(11):5062-72 PMID: 2481229
  5. Metabolism of orally administered ergosterol and 7-dehydrocholesterol in rats and lack of evidence for their vitamin D biological activity.
    J Nutr Sci Vitaminol (Tokyo). 1992 Feb;38(1):15-25 PMID: 1629783
  6. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis.
    J Immunol. 1992 Dec 15;149(12):4067-73 PMID: 1281200
  7. Isolation and characterization of immunosuppressive components of three mushrooms, Pisolithus tinctorius, Microporus flabelliformis and Lenzites betulina.
    Chem Pharm Bull (Tokyo). 1994 Mar;42(3):694-7 PMID: 8004718
  8. C/EBP beta regulation of the tumor necrosis factor alpha gene.
    J Clin Invest. 1994 Oct;94(4):1449-55 PMID: 7929820
  9. Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7673-8 PMID: 8755534
  10. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.
    Cell. 1997 May 2;89(3):331-40 PMID: 9150132
  11. Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK.
    Mol Cell Biol. 1997 Nov;17(11):6274-82 PMID: 9343388
  12. Nonsteroidal anti-inflammatory drugs, short-chain fatty acids, and reactive oxygen metabolism in human colorectal cancer cells.
    Biochim Biophys Acta. 1998 Mar 5;1401(3):277-88 PMID: 9540818
  13. p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6791-6 PMID: 9618491
  14. IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression.
    Cancer Res. 1998 Jul 1;58(13):2832-7 PMID: 9661898
  15. The human 2',5'-oligoadenylate synthetase locus is composed of three distinct genes clustered on chromosome 12q24.2 encoding the 100-, 69-, and 40-kDa forms.
    Genomics. 1998 Sep 15;52(3):267-77 PMID: 9790745
  16. Activation of the JAK-STAT pathway by reactive oxygen species.
    Am J Physiol. 1998 Dec;275(6 Pt 1):C1640-52 PMID: 9843726
  17. Isoform-specific induction of a human aldo-keto reductase by polycyclic aromatic hydrocarbons (PAHs), electrophiles, and oxidative stress: implications for the alternative pathway of PAH activation catalyzed by human dihydrodiol dehydrogenase.
    Cancer Res. 1999 Feb 1;59(3):607-14 PMID: 9973208
  18. Antitumor sterols from the mycelia of Cordyceps sinensis.
    Phytochemistry. 1999 Aug;51(7):891-8 PMID: 10423860
  19. A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with implications for therapy in rheumatoid arthritis.
    J Immunol. 2004 Dec 1;173(11):6928-37 PMID: 15557189
  20. Hemozoin induces macrophage chemokine expression through oxidative stress-dependent and -independent mechanisms.
    J Immunol. 2005 Jan 1;174(1):475-84 PMID: 15611273
  21. Ergosterol peroxide, an apoptosis-inducing component isolated from Sarcodon aspratus (Berk.) S. Ito.
    Biosci Biotechnol Biochem. 2005 Jan;69(1):212-5 PMID: 15665489
  22. Simvastatin attenuates expression of cytokine-inducible nitric-oxide synthase in embryonic cardiac myoblasts.
    J Biol Chem. 2005 Apr 8;280(14):13503-11 PMID: 15705589
  23. Medicinal mushroom modulators of molecular targets as cancer therapeutics.
    Appl Microbiol Biotechnol. 2005 Jun;67(4):453-68 PMID: 15726350
  24. 5alpha,8alpha-Epidioxy-22E-ergosta-6,9(11),22-trien-3beta-ol from an edible mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells.
    Biol Pharm Bull. 2006 Apr;29(4):755-9 PMID: 16595913
  25. Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator of transcription 1, 2, and 3 genes in colon tumor cells.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14007-12 PMID: 10570189
  26. Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter.
    J Biol Chem. 2000 Feb 18;275(7):5214-21 PMID: 10671569
  27. The use of mushroom glucans and proteoglycans in cancer treatment.
    Altern Med Rev. 2000 Feb;5(1):4-27 PMID: 10696116
  28. Transcriptional control of the human plasma membrane phospholipid scramblase 1 gene is mediated by interferon-alpha.
    Blood. 2000 Apr 15;95(8):2593-9 PMID: 10753839
  29. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages.
    J Biol Chem. 2000 May 26;275(21):16023-9 PMID: 10821856
  30. The reactive oxygen species--and Michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene.
    J Biol Chem. 2001 Jan 26;276(4):2890-7 PMID: 11060293
  31. Transcriptional response of a human colon adenocarcinoma cell line to sodium butyrate.
    Biochem Biophys Res Commun. 2001 Aug 3;285(5):1280-9 PMID: 11478796
  32. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines.
    Cancer Res. 2001 Aug 15;61(16):6120-30 PMID: 11507062
  33. New sterols from two edible mushrooms, Pleurotus eryngii and Panellus serotinus.
    Chem Pharm Bull (Tokyo). 2002 Apr;50(4):551-3 PMID: 11964010
  34. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray.
    Cancer Res. 2002 Sep 15;62(18):5196-203 PMID: 12234984
  35. HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells.
    Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):58-63 PMID: 12524225
  36. Inhibition of IFN-gamma-mediated inducible nitric oxide synthase induction by the peroxisome proliferator-activated receptor gamma agonist, 15-deoxy-delta 12,14-prostaglandin J2, involves inhibition of the upstream Janus kinase/STAT1 signaling pathway.
    J Immunol. 2003 Jul 15;171(2):979-88 PMID: 12847270
  37. Vitamin D and vitamin D analogs as cancer chemopreventive agents.
    Nutr Rev. 2003 Jul;61(7):227-38 PMID: 12918875
  38. Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae.
    Br J Pharmacol. 2003 Nov;140(5):895-906 PMID: 14504132
  39. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells.
    Oncogene. 2003 Nov 13;22(51):8271-82 PMID: 14614451
  40. Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production.
    Toxicol Appl Pharmacol. 2004 Jun 1;197(2):84-95 PMID: 15163544
  41. Retinoic acid-inducible gene-I is induced by interferon-gamma and regulates the expression of interferon-gamma stimulated gene 15 in MCF-7 cells.
    Biochem Cell Biol. 2004 Jun;82(3):401-5 PMID: 15181474
  42. P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells.
    Cancer Res. 2004 Sep 1;64(17):6296-303 PMID: 15342418
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0706972
Email
kobori@affrc.go.jp
Published
2007-01-00
Epub
2006-00-11
Pages
209-19
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2042906
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0706972 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2