@Article{096504019X15736439848765,
AUTHOR = {Nahathai Dukaew, Teruaki Konishi, Kongthawat Chairatvit, Narongchai Autsavapromporn, 
Noppamas Soonthornchareonnon, Ariyaphong Wongnoppavich},
TITLE = {Enhancement of Radiosensitivity by Eurycomalactone in Human  NSCLC Cells Through G<sub>2</sub> /M Cell Cycle Arrest and Delayed  DNA Double-Strand Break Repair},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {2},
PAGES = {161--175},
URL = {http://www.techscience.com/or/v28n2/48541},
ISSN = {1555-3906},
ABSTRACT = {Radiotherapy (RT) is an important treatment for non-small cell lung cancer (NSCLC). However, the major 
obstacles to successful RT include the low radiosensitivity of cancer cells and the restricted radiation dose, 
which is given without damaging normal tissues. Therefore, the sensitizer that increases RT efficacy without 
dose escalation will be beneficial for NSCLC treatment. Eurycomalactone (ECL), an active quassinoid isolated 
from <i>Eurycoma longifolia</i> Jack, has been demonstrated to possess anticancer activity. In this study, we aimed 
to investigate the effect of ECL on sensitizing NSCLC cells to X-radiation (X-ray) as well as the underlying 
mechanisms. The results showed that ECL exhibited selective cytotoxicity against the NSCLC cells A549 and 
COR-L23 compared to the normal lung fibroblast. Clonogenic survival results indicated that ECL treatment 
prior to irradiation synergistically decreased the A549 and COR-L23 colony number. ECL treatment reduced 
the expression of cyclin B1 and CDK1/2 leading to induce cell cycle arrest at the radiosensitive G<sub>2</sub>
/M phase. 
Moreover, ECL markedly delayed the repair of radiation-induced DNA double-strand breaks (DSBs). In A549 
cells, pretreatment with ECL not only delayed the resolving of radiation-induced -H2AX foci but also blocked 
the formation of 53BP1 foci at the DSB sites. In addition, ECL pretreatment attenuated the expression of DNA 
repair proteins Ku-80 and KDM4D in both NSCLC cells. Consequently, these effects led to an increase in 
apoptosis in irradiated cells. Thus, ECL radiosensitized the NSCLC cells to X-ray via G2
/M arrest induction and 
delayed the repair of X-ray-induced DSBs. This study offers a great potential for ECL as an alternative safer 
radiosensitizer for increasing the RT efficiency against NSCLC.},
DOI = {10.3727/096504019X15736439848765}
}