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.