Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation.
Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardioprotection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-kappaB) 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-kappaB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 microM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-kappaB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G0/G1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-kappaB inhibition and S-phase arrest.