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Kuwahara, Y., Oikawa, T., Ochiai, Y., Roudkenar, M.H., Fukumoto, M., Shimura, T., Ohtake, Y., Ohkubo, Y., Mori, S., Uchiyama, Y. and Fukumoto, M. (2011) Enhancement of Autophagy Is a Potential Modality for Tumors Refractory to Radiotherapy. Cell Death and Disease, 30, e177.

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• TITLE: Carbon-Ion Beams Efficiently Induce Cell Killing in X-Ray Resistant Human Squamous Tongue Cancer Cells

  AUTHORS: Akihisa Takahashi, Hongyu Ma, Akiko Nakagawa, Yukari Yoshida, Tatsuaki Kanai, Tatsuya Ohno, Yoshikazu Kuwahara, Manabu Fukumoto, Takashi Nakano

  KEYWORDS: Carbon-Ion Beams, X-Ray Resistant Cells, Cell Survival and Death Signaling, Cancer Stem-Like Cells

  JOURNAL NAME: International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, Vol.3 No.3, July 25, 2014

  ABSTRACT: In order to see whether carbon ion (C-ion) beams have a biological advantage over X-rays, studies were designed to examine the effects of C-ion beams on radiosensitivity in X-ray resistant cells. Clinically relevant X-ray resistant SAS-R cells derived from human tongue cancer SAS cells were used. The cells were exposed to X-rays or Spread-Out Bragg peak (SOBP) beam C-ions. Cell survival was measured using a modified high-density survival assay. Cell survival signaling and cell death signaling were analyzed using flow cytometry. The cells were labeled with putative cancer stem cell markers such as CD44 and CD326. SAS-R cells were 1.6 times more radioresistant than SAS cells after exposure to X-rays. Cell survival was similar in each cell line after exposure to C-ion beams. SAS-R cells displayed enhanced cell survival signaling when compared to SAS cells under normal conditions. On the other hand, the phosphorylation of AKT-related proteins decreased and polycaspase activities were enhanced when cells were irradiated with C-ion beams in both cell lines. More CD44 and CD326 positive cells were seen in SAS-R cells than in SAS cells. Moreover, the marker positive cell numbers significantly decreased after exposure to C-ion beams when compared to X-rays at iso-survival doses in SAS-R cells. C-ion beams efficiently induced cell killing in X-ray resistant cells which displayed activated cell survival signaling and contained more numerous cancer stem-like cells.