title: Fractionated radiation-induced nitric oxide promotes expansion of glioma stem-like cells.
abstract: Glioblastoma remains an incurable brain disease due to the prevalence of its recurrence. Considerable evidence suggests that glioma stem-like cells are responsible for glioma relapse after treatment, which commonly involves ionizing radiation. Here, we found that fractionated ionizing radiation (2 Gy/day for 3 days) induced glioma stem-like cell expansion and resistance to anticancer treatment such as cisplatin (50 μM) or taxol (500 nM), or by ionizing radiation (10 Gy) in both glioma cell lines (U87, U373) and patient-derived glioma cells. Of note, concomitant increase of nitric oxide production occurred with the radiation-induced increase of the glioma stem-like cell population through upregulation of inducible nitric oxide synthase (iNOS). In line with this observation, downregulation of iNOS effectively reduced the glioma stem-like cell population and decreased resistance to anticancer treatment. Collectively, our results suggest that targeting iNOS in combination with ionizing radiation might increase the efficacy of radiotherapy for glioma treatment.
authors.affiliation: Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Rae-Kwon
authors.initials: RK
authors.lastname: Kim
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Cui
authors.forename: Eunji
authors.initials: E
authors.lastname: Hwang
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lim
authors.forename: Ki-Chun
authors.initials: KC
authors.lastname: Yoo
authors.forename: Ga-Haeng
authors.initials: GH
authors.lastname: Lee
authors.forename: Joo-Mi
authors.initials: JM
authors.lastname: Yi
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D015854:Up-Regulation
chemical_list: D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II