title: A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/β-catenin signaling pathway.
abstract: Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, and interferon-α) are only of marginal benefit. There is an urgent need for more effective treatments for meningioma patients who have failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that have anti-tumorgenic properties and cause cell death in meningioma cells in vitro. Due to its ease of administration, long-term tolerability, and low incidence of long-term side effects, we explored its potential as a therapeutic agent against meningiomas by examining their efficacy in vitro against meningioma cells. Treatment effects were assessed using MTT assay, Western blot analysis, caspases assay, and DNA fragmentation assay. Results indicated that treatments of IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 β (GSK3β) via inhibition of the Wnt5/β-catenin pathway. These drugs did not induce apoptosis in normal human neurons. Other events in apoptosis included downregulation of tetraspanin protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression apoptotic factors (Bax and caspase-3). These results provide preliminary strong evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol, Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade meningiomas as a therapeutic agent, and suggests that further in vivo studies are necessary to explore its potential as a therapeutic agent against malignant meningiomas.
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA. dasa@musc.edu.|Department of Neurosurgery, Neuro-oncology Division, MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina at Charleston, Charleston, SC, 29425, USA. dasa@musc.edu.
authors: Arabinda
authors: A
authors: Das
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Rickey
authors: R
authors: Miller
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Philip
authors: P
authors: Lee
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Chrysanthe Alyssa
authors: CA
authors: Holden
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Scott M
authors: SM
authors: Lindhorst
authors: Department of Radiation Oncology, School of Medicine, Washington University, St. Louis, MO, 63110, USA.
authors: Jerry
authors: J
authors: Jaboin
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: William A
authors: WA
authors: Vandergrift
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.|Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
authors: Naren L
authors: NL
authors: Banik
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.|Department of Neurological Surgery, Wexner Medical College, Ohio State University, Columbus, OH, 43210, USA.
authors: Pierre
authors: P
authors: Giglio
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Abhay K
authors: AK
authors: Varma
authors: Department of Neurology and Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Jeffery J
authors: JJ
authors: Raizer
authors: Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Sunil J
authors: SJ
authors: Patel
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002396:Catechols / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005233:Fatty Alcohols / Q000008:administration & dosage* / Q000737:chemistry; D047309:Flavones / Q000008:administration & dosage* / Q000737:chemistry; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007810:Lanosterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D036701:Limonins / Q000008:administration & dosage* / Q000737:chemistry; D008579:Meningioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000737:chemistry; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C584306:3,7-dioxolanosta-8,24-dien-26-oic acid; D002396:Catechols; D005233:Fatty Alcohols; D047309:Flavones; D006538:Heptanoic Acids; D036701:Limonins; D012717:Sesquiterpenes; D014315:Triterpenes; D007810:Lanosterol; C403304:zerumbone; C515005:ganoderic acid A; C007845:gingerol; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C059006:tangeretin; C001546:limonin
keywords: Apoptosis; Catenin; Ginger; Lemon; Meningioma; Mushroom; Wnt