Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation

Sun Hye Shin, Mi Jin Yoon, Mira Kim, Jong Il Kim, Su Jae Lee, Yun Sil Lee, Sangwoo Bae

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Selenium has been associated with anticancer activity by affecting multiple cellular processes. We reasoned that the simultaneous modulation of multiple radioresponse regulators by selenium should increase radiosensitivity if selenium is combined with radiation in cancer therapy. Therefore, we explored the possibility of whether we could obtain an enhancement of radiosensitivity by the combination of selenium and ionizing radiation. We used two human lung cancer cell lines, NCI-H460 and H1299, as well as a human diploid lung fibroblast, WI-38, as the normal cell counterpart. The combined treatment of the cancer cell lines with Seleno-methionine and ionizing radiation resulted in increased cell killing as assessed by clonogenic survival assay whereas it had little effect on the normal diploid WI-38 cells. The increased radiosensitivity in the cancer cells was correlated with the attenuation of the key proteins involved in either cell survival signaling [Akt, EGFR (epidermal growth factor receptor), ErbB2 and Raf1] or DNA damage response (Mre11, Rad50, Nbs1, Ku80, 53BP1 and DNAPK). The attenuation of the proteins by the selenium compound was possibly caused by the effect on transcription and on protein stability since selenium treatment decreased both the RNA transcript and the protein stability of EGFR and DNAPK. By contrast, Seleno-L-methionine had no effect on the protein profile of a normal diploid fibroblast which is consistent with an intact radiosensitivity. These data provide possible clinical applications, as selenium selectively enhanced the radiosensitivity of the tumor cells whereas that of the normal cells was unaffected. Moreover, the selective decrease of cell proliferation signaling in tumor cells but not in normal cells should facilitate the repopulation of normal cells required for healing during radiation therapy. On the whole, the results suggest that the cancer preventive activity of selenium can be combined with ionizing radiation to improve the control of lung cancer.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalOncology Reports
Volume17
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Cell proliferation
  • DNA double strand break repair factors
  • Multi-target approach
  • Radiosensitivity
  • Selenium

Fingerprint

Dive into the research topics of 'Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation'. Together they form a unique fingerprint.

Cite this