A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/β-catenin signaling pathway

• Published in: Tumor biology Vol. 36; no. 9; pp. 7027 - 7034
• Main Authors: Das, Arabinda, Miller, Rickey, Lee, Philip, Holden, Chrysanthe Alyssa, Lindhorst, Scott M., Jaboin, Jerry, Vandergrift, William A., Banik, Naren L., Giglio, Pierre, Varma, Abhay K., Raizer, Jeffery J., Patel, Sunil J.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-09-2015
• Subjects: Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cancer Research; Catechols - administration & dosage; Catechols - chemistry; Cell Line, Tumor; Citrus; DNA Fragmentation - drug effects; Fatty Alcohols - administration & dosage; Fatty Alcohols - chemistry; Flavones - administration & dosage; Flavones - chemistry; Glycogen Synthase Kinase 3 - biosynthesis; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 beta; Heptanoic Acids - administration & dosage; Heptanoic Acids - chemistry; Humans; Lanosterol - administration & dosage; Lanosterol - analogs & derivatives; Lanosterol - chemistry; Limonins - administration & dosage; Limonins - chemistry; Meningioma - drug therapy; Meningioma - genetics; Meningioma - pathology; Research Article; Sesquiterpenes - administration & dosage; Sesquiterpenes - chemistry; Triterpenes - administration & dosage; Triterpenes - chemistry; Wnt Signaling Pathway - drug effects; Mushroom; Ginger; Wnt; Catenin; Lemon; Meningioma; Apoptosis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3388-0

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.