@misc{oai:repo.qst.go.jp:00076613,
 author = {Dukaew, Nahathai and Autsavapromporn, Narongchai and Konishi, Teruaki and Chairatvit, Kongthawat and Soonthornchareonnon, Noppamas and Konishi, Teruaki},
 month = {Aug},
 note = {Background: Radiotherapy (RT) is an important treatment for non-small cell lung cancer (NSCLC). However, the low radiation sensitivity of lung cancer cells turns out to be one major obstacle to RT efficacy. Therefore, application of a sensitizer that increases radiation effect without dose escalation will be beneficial for NSCLC treatment. Eurycoma longifolia Jack is an herbal medicinal plant of South-East Asian origin. The anticancer activity of this plant has also been proved scientifically. Interestingly, among all active quassinoids isolated
from E. longifolia, eurycomalactone (ECL) exhibited most potent cytotoxicity against lung cancer cells. Aim: This study aimed to investigate whether ECL would enhance the radiosensitivity of NSCLC cells. Methods: Cytotoxicity of ECL on NSCLC cell lines (A549, Calu-1) and human lung fibroblast (WI-38) was
determined using MTT assay. The effects of ECL combined with X-rays on clonogenicity, cell cycle progression, cell apoptosis and the G2/M regulatory proteins expression were analyzed with clonogenic assay, flow cytometry and immunoblotting, respectively. DNA double-strand break (DSB) and the repair
capacity were evaluated by immunofluorescence and immunoblotting.
Results/Conclusions: ECL exhibited selective cytotoxicity against A549 cells as compared to the normal one. ECL treatment prior to irradiation synergistically decreased the A549 colony formation, suggesting the enhancement of radiosensitivity by ECL. Moreover, ECL was able to reduce expression of CDK1/2 and CyclinB1 leading to cell cycle arrest at radiosensitive G2/M phase. ECL markedly delayed the repair of radiation-induced DSB. Pre-treatment with ECL followed by X-ray not only delayed the γ-H2AX foci resolving and blocked the 53BP1 foci formation at the DSB sites, but also attenuated expression of DNA repair proteins, Ku80 and KDM4D. Consequently, these effects led to an increase in the cell apoptosis after irradiation. This study offers a great potential for ECL as an alternative safer radiosensitizer to improve the RT efficacy of NSCLC., 16th International Congress of Radiation Research},
 title = {Radiosensitivity Enhancement by Eurycomalactone in Lung Adenocarcinoma via G2/M Cell Cycle Arrest Induction and Delay of DNA Double-strand Break Repair},
 year = {2019}
}