PMID- 25409926 OWN - NLM STAT- MEDLINE DCOM- 20150129 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1853 IP - 1 DP - 2015 Jan TI - Biphasic effects of luteolin on interleukin-1beta-induced cyclooxygenase-2 expression in glioblastoma cells. PG - 126-35 LID - S0167-4889(14)00369-3 [pii] LID - 10.1016/j.bbamcr.2014.10.010 [doi] AB - Success in developing therapeutic approaches to target brain tumor-associated inflammation in patients has been limited. Given that the inflammatory microenvironment is a hallmark signature of solid tumor development, anti-inflammatory targeting strategies have been envisioned as preventing glioblastoma initiation or progression. Consumption of foods from plant origin is associated with reduced risk of developing cancers, a chemopreventive effect that is, in part, attributed to their high content of phytochemicals with potent anti-inflammatory properties. We explored whether luteolin, a common flavonoid in many types of plants, may inhibit interleukin (IL)-1beta function induction of the inflammation biomarker cyclooxygenase (COX)-2. We found that IL-1beta triggered COX-2 expression in U-87 glioblastoma cells and synergized with luteolin to potentiate or inhibit that induction in a biphasic manner. Luteolin pretreatment of cells inhibited IL-1beta-mediated phosphorylation of inhibitor of kappaB, nuclear transcription factor-kappaB (NF-kappaB) p65, extracellular signal-regulated kinase-1/2, and c-Jun amino-terminal kinase in a concentration-dependent manner. Luteolin also inhibited AKT phosphorylation and survivin expression, while it triggered both caspase-3 cleavage and expression of glucose-regulated protein 78. These effects were all potentiated by IL-1beta, in part through increased nuclear translocation of NF-kappaB p65. Finally, luteolin was able to reduce IL-1 receptor gene expression, and treatment with IL-1 receptor antagonist or gene silencing of IL-1 receptor prevented IL-1beta/luteolin-induced COX-2 expression. Our results document a novel adaptive cellular response to luteolin, which triggers anti-survival and anti-inflammatory mechanisms that contribute to the chemopreventive properties of this diet-derived molecule. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Lamy, Sylvie AU - Lamy S AD - Laboratoire d'Oncologie Moleculaire, Centre de Recherche BioMed, Universite du Quebec a Montreal, C.P. 8888, Succ. Centre-ville, Montreal, Quebec H3C 3P8, Canada. Electronic address: lamy.sylvie@uqam.ca. FAU - Moldovan, Paula Liana AU - Moldovan PL AD - Laboratoire d'Oncologie Moleculaire, Centre de Recherche BioMed, Universite du Quebec a Montreal, C.P. 8888, Succ. Centre-ville, Montreal, Quebec H3C 3P8, Canada. Electronic address: moldovan.paula_liana@courrier.uqam.ca. FAU - Ben Saad, Aroua AU - Ben Saad A AD - Laboratoire d'Oncologie Moleculaire, Centre de Recherche BioMed, Universite du Quebec a Montreal, C.P. 8888, Succ. Centre-ville, Montreal, Quebec H3C 3P8, Canada. Electronic address: ben_saad.aroua@courrier.uqam.ca. FAU - Annabi, Borhane AU - Annabi B AD - Laboratoire d'Oncologie Moleculaire, Centre de Recherche BioMed, Universite du Quebec a Montreal, C.P. 8888, Succ. Centre-ville, Montreal, Quebec H3C 3P8, Canada. Electronic address: annabi.borhane@uqam.ca. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141018 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Interleukin-1beta) RN - 0 (Receptors, Interleukin-1) RN - 0 (Transcription Factor RelA) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - KUX1ZNC9J2 (Luteolin) SB - IM MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cyclooxygenase 2/*genetics MH - Gene Expression Regulation, Enzymologic/drug effects MH - Glioblastoma/*enzymology MH - Humans MH - Interleukin-1beta/*pharmacology MH - Luteolin/*pharmacology MH - MAP Kinase Signaling System/physiology MH - Receptors, Interleukin-1/physiology MH - Transcription Factor RelA/metabolism OTO - NOTNLM OT - COX-2 OT - Glioblastoma OT - Inflammation OT - Interleukin-1 OT - Luteolin OT - NF-kappaB EDAT- 2014/11/21 06:00 MHDA- 2015/01/30 06:00 CRDT- 2014/11/21 06:00 PHST- 2014/05/28 00:00 [received] PHST- 2014/10/10 00:00 [revised] PHST- 2014/10/13 00:00 [accepted] PHST- 2014/11/21 06:00 [entrez] PHST- 2014/11/21 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] AID - S0167-4889(14)00369-3 [pii] AID - 10.1016/j.bbamcr.2014.10.010 [doi] PST - ppublish SO - Biochim Biophys Acta. 2015 Jan;1853(1):126-35. doi: 10.1016/j.bbamcr.2014.10.010. Epub 2014 Oct 18.