Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation

Bong Cho Kim, Hee Jung Yoo, Hyung Chul Lee, Kyoung Ah Kang, Seung Hee Jung, Hae June Lee, Minyoung Lee, Seungwoo Park, Young Hoon Ji, Yun Sil Lee, Young Gyu Ko, Jae Seon Lee

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13 Citations (Scopus)

Abstract

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated â-galactosidase (SA-β-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro. We demonstrated the beneficial tumor suppressive role of ionizing radiation (IR)-induced premature senescence in vitro and in vivo. FR inhibited tumor growth via induction of premature senescence as effectively as an equivalent SR dose (.6 Gy). In addition, CD and eEF1 were valuable biomarkers of cellular senescence in either SR- or RF-exposed carcinoma cells or xenograft mice. Our results suggest that 2 Gy of a conventional RT regime could achieve a better clinical outcome if premature senescence could be increased through an improved understanding of its molecular action mechanism.

Original languageEnglish
Pages (from-to)2229-2235
Number of pages7
JournalOncology reports
Volume31
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Biomarker
  • Cancer
  • Fractionated irradiation
  • Premature senescence
  • Single irradiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kim, B. C., Yoo, H. J., Lee, H. C., Kang, K. A., Jung, S. H., Lee, H. J., Lee, M., Park, S., Ji, Y. H., Lee, Y. S., Ko, Y. G., & Lee, J. S. (2014). Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation. Oncology reports, 31(5), 2229-2235. https://doi.org/10.3892/or.2014.3069