title: COX-2 regulates the proliferation of glioma stem like cells.
abstract: Cancer stem-like cells (CSCs) possessing features of neural precursor cells (NPC) influence initiation, recurrence and chemoresistance of glioblastoma multiforme (GBM). As inflammation is crucial for glioblastoma progression we investigated the effect of chronic IL-1β treatment on CSCs derived from glioblastoma cell line U87MG. Exposure to IL-1β for 10 days increased (i) accumulation of 8-OHdG - a key biomarker of oxidative DNA damage; (ii) DNA damage response (DDR) indicators γH2AX, ATM and DNA-PK; (iii) nuclear and cytoplasmic p53 and COX-2 levels and (iv) interaction between COX-2 and p53. Despite upregulating p53 expression IL-1β had no effect on cell cycle progression, apoptosis or self renewal capacity of CSCs. COX-2 inhibitor Celecoxib reduced self renewal capacity and increased apoptosis of both control and IL-1β treated CSCs. Therefore the ability of COX-2 to regulate proliferation of CSCs irrespective of exposure to IL-1β, warrants further investigation of COX-2 as a potential anti-glioma target.
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122 050, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.forename: Deobrat
authors.initials: D
authors.lastname: Dixit
authors.forename: Sadashib
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ellora
authors.initials: E
authors.lastname: Sen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004273:DNA, Neoplasm; C468783:H2AX protein, human; D006657:Histones; D053583:Interleukin-1beta; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051546:Cyclooxygenase 2; D053148:Caspase 3; D003849:Deoxyguanosine