Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardioprotection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-kappa B) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using propidium iodide staining and flow cytometry. An ELISA-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-kappa B. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 mu M. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-kappa B, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G(0)/G(1) phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-kappa B inhibition and S-phase arrest.
