Open Access
ARTICLE
Enhancement of Radiosensitivity by Eurycomalactone in Human NSCLC Cells Through G2 /M Cell Cycle Arrest and Delayed DNA Double-Strand Break Repair
Nahathai Dukaew*†, Teruaki Konishi‡§, Kongthawat Chairatvit¶, Narongchai Autsavapromporn#,
Noppamas Soonthornchareonnon**, Ariyaphong Wongnoppavich†
* Graduate/PhD’s Degree Program in Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
† Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
‡ Single Cell Radiation Biology Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological
Science and Technology (QST), Chiba, Japan
§ Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences (NIRS), Chiba, Japan
¶ Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
# Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
** Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
Oncology Research 2020, 28(2), 161-175. https://doi.org/10.3727/096504019X15736439848765
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
Eurycoma longifolia 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
2
/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.
Keywords
Cite This Article
Dukaew, N., Konishi, T., Chairatvit, K., Autsavapromporn, N., Soonthornchareonnon,
. et al. (2020). Enhancement of Radiosensitivity by Eurycomalactone in Human NSCLC Cells Through G
2 /M Cell Cycle Arrest and Delayed DNA Double-Strand Break Repair.
Oncology Research, 28(2), 161–175. https://doi.org/10.3727/096504019X15736439848765