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