Toxicological effects of NCKU-21, a phenanthrene derivative, on cell growth and migration of A549 and CL1-5 human lung adenocarcinoma cells

Hsien Feng Liao, Chun Hsu Pan, Pei Yu Chou, Yi Fong Chen, Tian Shung Wu, Ming Jyh Sheu, Chieh Hsi Wu

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

Background: Chemotherapy insensitivity continues to pose significant challenges for treating non-small cell lung cancer (NSCLC). The purposes of this study were to investigate whether 3,6-dimethoxy-1,4,5,8-phenanthrenetetraone (NCKU-21) has potential activity to induce effective toxicological effects in different ethnic NSCLC cell lines, A549 and CL1-5 cells, and to examine its anticancer mechanisms. Methods: Mitochondrial metabolic activity and the cell-cycle distribution were analyzed using an MTT assay and flow cytometry in NCKU-21-treated cells. NCKU-21-induced cell apoptosis was verified by Annexin V-FITC/propidium iodide (PI) double-staining and measurement of caspase-3 activity. Western blotting and wound-healing assays were applied to respectively evaluate regulation of signaling pathways and cell migration by NCKU-21. Molecular interactions between target proteins and NCKU-21 were predicted and performed by molecular docking. A colorimetric screening assay kit was used to evaluate potential regulation of matrix metalloproteinase-9 (MMP-9) activity by NCKU-21. Results: Results indicated that NCKU-21 markedly induced cytotoxic effects that reduced cell viability via cell apoptosis in tested NSCLC cells. Activation of AMP-activated protein kinase (AMPK) and p53 protein expression also increased in both NSCLC cell lines stimulated with NCKU-21. However, repression of PI3K-AKT activation by NCKU-21 was found in CL1-5 cells but not in A549 cells. In addition, increases in phosphatidylserine externalization and caspase-3 activity also confirmed the apoptotic effect of NCKU-21 in both NSCLC cell lines. Moreover, cell migration and translational levels of the gelatinases, MMP-2 and MMP-9, were obviously reduced in both NSCLC cell lines after incubation with NCKU-21. Experimental data obtained from molecular docking suggested that NCKU-21 can bind to the catalytic pocket of MMP-9. However, the in vitro enzyme activity assay indicated that NCKU-21 has the potential to increase MMP-9 activity. Conclusions: Our results suggest that NCKU-21 can effectively reduce cell migration and induce apoptosis in A549 and CL1-5 cells, the toxicological effects of which may be partly modulated through PI3K-AKT inhibition, AMPK activation, an increase in the p53 protein, and gelatinase inhibition.
原文英語
文章編號e0185021
期刊PLoS ONE
12
發行號9
DOIs
出版狀態已發佈 - 9月 2017

ASJC Scopus subject areas

  • 多學科

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