Table of Content

Open Access iconOpen 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 G2 /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 G2 /M Cell Cycle Arrest and Delayed DNA Double-Strand Break Repair. Oncology Research, 28(2), 161–175.



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 568

    View

  • 393

    Download

  • 0

    Like

Share Link