title: Knockdown of cytoglobin expression sensitizes human glioma cells to radiation and oxidative stress.
abstract: Cytoglobin is a recently identified vertebrate globin whose functions include scavenging reactive oxygen and nitrosative species. In tumor cells, CYGB may function as a tumor suppressor gene. Here we show that knockdown of cytoglobin expression can sensitize human glioma cells to oxidative stress induced by chemical inhibitors of the electron transport chain and as well can increase cellular radiosensitivity. When treated with antimycin A, an inhibitor of the mitochondrial electron transport chain, cytoglobin-deficient cells showed significantly higher H₂O₂ levels, whereas H₂O₂ levels were significantly reduced in cytoglobin-overexpressing cells. In addition, cytoglobin knockdown significantly decreased the doubling time of glioma cell lines, consistent with a putative tumor suppressor function. These finding suggest that modulating cytoglobin levels may be a promising treatment strategy for sensitizing human glioma cells to oxidative stress that is induced by ionizing radiation, certain chemotherapies and ischemia-reperfusion.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jingye
authors.initials: J
authors.lastname: Fang
authors.forename: Ivy
authors.initials: I
authors.lastname: Ma
authors.forename: Joan
authors.initials: J
authors.lastname: Allalunis-Turner
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D015687:Cell Hypoxia / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D000078842:Cytoglobin; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000473:pathology*; D005914:Globins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics* / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D017382:Reactive Oxygen Species; D005914:Globins