| RRC ID |
60693
|
| 著者 |
Dukaew N, Konishi T, Chairatvit K, Autsavapromporn N, Soonthornchareonnon N, Wongnoppavich A.
|
| タイトル |
Enhancement of Radiosensitivity by Eurycomalactone in Human NSCLC Cells Through G₂/M Cell Cycle Arrest and Delayed DNA Double-Strand Break Repair.
|
| ジャーナル |
Oncol Res
|
| 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 γ-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.
|
| 巻・号 |
28(2)
|
| ページ |
161-175
|
| 公開日 |
2020-3-27
|
| DOI |
10.3727/096504019X15736439848765
|
| PMID |
31727206
|
| PMC |
PMC7851521
|
| MeSH |
A549 Cells
Apoptosis / drug effects
CDC2 Protein Kinase / genetics*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / radiotherapy*
Cell Cycle Checkpoints / drug effects
Cell Cycle Checkpoints / radiation effects
Cell Line, Tumor
Cell Survival / drug effects
Cyclin B1 / genetics
DNA Breaks, Double-Stranded / drug effects
DNA Breaks, Double-Stranded / radiation effects
DNA Repair / drug effects
Eurycoma / chemistry
G2 Phase Cell Cycle Checkpoints / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lactones / pharmacology*
Radiation Tolerance / drug effects
Radiation-Sensitizing Agents / pharmacology
|
| IF |
4.949
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
WI-38(RCB0702)
A549(RCB0098) |
