title: Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.
abstract: Interleukin (IL)-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF)-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.
authors.affiliation: Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.affiliation: Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
authors.affiliation: Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hütten
authors.affiliation: Department of Orthopedics, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Röpke
authors.affiliation: Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.affiliation: Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Nass
mesh_terms: D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A; D053592:Interleukin-1 Receptor-Associated Kinases; D003474:Curcumin