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.
Liao
Hui-Fen
HF
Department of Molecular Biology and Biochemistry, National Chiayi University, Taiwan.
Kuo
Cheng-Deng
CD
Yang
Yuh-Cheng
YC
Lin
Chin-Ping
CP
Tai
Hung-Chi
HC
Chen
Yu-Yawn
YY
Chen
Yu-Jen
YJ
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism* / Q000528:radiation effects; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
D016328:NF-kappa B; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D000077185:Resveratrol