Mitigation of radiation-induced damage by targeting EGFR in noncancerous human epithelial cells

Radiat Res. 2013 Sep;180(3):259-67. doi: 10.1667/RR3371.1. Epub 2013 Aug 6.


Methyl-2-cyano-3,12 dioxoolean-1,9 diene-28-oate (CDDO-Me) is an antioxidative, anti-inflammatory modulator, which activates the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. While CDDO-Me has radioprotective activity through Nrf2 activation in vitro and in vivo, its ability to mitigate radiation-induced damage when provided after irradiation has not been studied. Here we investigated whether CDDO-Me mitigates ionizing radiation (IR)-induced DNA damage in immortalized normal human colonic epithelial cells (HCECs) and bronchial epithelial cells (HBECs). DNA damage and clonogenic survival were assessed after treatment with CDDO-Me postirradiation. We observed that treatment with CDDO-Me within 30 min after irradiation improved both DNA damage repair and clonogenic survival independently of Nrf2. CDDO-Me activates the epidermal growth factor receptor (EGFR) related DNA repair responses. In the presence of CDDO-Me, EGFR is phosphorylated and translocates into the nucleus where it interacts with DNA-PKcs. CDDO-Me-mediated mitigation activity can be abrogated through depletion of EGFR, ectopic overexpression of mutant EGFR or inhibition of DNA-PKcs. While post-treatment of CDDO-Me protected noncancerous HCECs and HBECs against IR, cancer cells (HCT116 and MCF7) were not protected by CDDO-Me. These results suggest that targeting EGFR using CDDO-Me is a promising radiation mitigator with potential utility for first responders to nuclear accidents.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bronchi / cytology
  • Bronchi / metabolism
  • Bronchi / radiation effects*
  • Cell Line, Tumor
  • Cells, Cultured
  • Colon / cytology
  • Colon / metabolism
  • Colon / radiation effects*
  • DNA Damage
  • DNA Repair
  • Epithelial Cells / radiation effects
  • ErbB Receptors / metabolism
  • ErbB Receptors / radiation effects*
  • Humans


  • ErbB Receptors