title: Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells.
abstract: Carbon-ion radiotherapy (CIRT) holds promise in the treatment of glioblastoma, an aggressive X-ray-resistant brain tumor. However, since glioblastoma cells show a highly invasive nature, carbon-ion (C-ion) irradiation of normal tissues surrounding the tumor is inevitable. Recent studies have revealed the existence of neural stem cells in the adult brain. Therefore, the damaging effect of C-ion beams on the neural stem cells has to be carefully considered in the treatment planning of CIRT. Here, we investigated the growth and death mode of human neural stem cells (hNSCs) and glioblastoma A172 cells after X-ray or C-ion beam irradiation. The X-ray dose resulting in a 50% growth rate (D(50)) was 0.8 Gy in hNSCs and 3.0 Gy in A172 cells, while the D(50) for C-ion beams was 0.4 Gy in hNSCs and 1.6 Gy in A172 cells; the relative biological effectiveness value of C-ion beams was 2.0 in hNSCs and 1.9 in A172 cells. Importantly, both X-rays and C-ion beams preferentially induced apoptosis, not necrosis, in hNSCs; however, radiation-induced apoptosis was less evident in A172 cells. The apoptosis-susceptible nature of the irradiated hNSCs was associated with prolonged upregulation of phosphorylated p53, whereas the apoptosis-resistant nature of A172 cells was associated with a high basal level of nuclear factor kappa B expression. Taken together, these data indicate that apoptosis is the major cell death pathway in hNSCs after irradiation. The high sensitivity of hNSCs to C-ion beams underscores the importance of careful target volume delineation in the treatment planning of CIRT for glioblastoma.
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Isono
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan yyukari@gunma-u.ac.jp.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan Advanced Scientific Research Leaders Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D017209:Apoptosis; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology*; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000473:pathology*; D063193:Heavy Ion Radiotherapy; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000528:radiation effects*; D010766:Phosphorylation; D012062:Relative Biological Effectiveness; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014965:X-Rays
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002244:Carbon
keywords: apoptosis; carbon-ion (C-ion) beams; glioblastoma; neural stem cells; radiosensitivity