Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe

• Amornwichet, Napapat

• Oike, Takahiro

• Shibata, Atsushi

• Ogiwara, Hideaki

• Tsuchiya, Naoto

• Yamauchi, Motohiro

• Saitoh, Yuka

• Sekine, Ryota

• Isono, Mayu

• Yoshida, Yukari

• Ohno, Tatsuya

• Kohno, Takashi

• Nakano, Takashi

• Peiwen Fei

  editor

Abstract

Background and Purpose: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies.Copyright: Materials and Methods: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/ + and p53-/-, respectively) were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA doublestrand breaks (DSBs) by immunostaining of phosphorylated H2AX (γH2AX), and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3. Results: The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring longretained DSBs at 24 h post-irradiation. Conclusions: Efficient induction of mitotic catastrophe in apoptosis-resistant p53- deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.

PLoS ONE, 9(12), e115121; 2014

Journal

• PLoS ONE

  PLoS ONE 9 (12), e115121-, 2014-12-22

  Public Library of Science

Keywords

• Multidisciplinary

Details

• CRID: 1050287297275311744
• NII Article ID: 120006986291
• ISSN: 19326203
• DOI: 10.1371/journal.pone.0115121
• HANDLE: 10069/35031
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/5937
• Web Site: http://dx.plos.org/10.1371/journal.pone.0115121
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN