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https://ir.cnu.edu.tw/handle/310902800/29728
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| Title: | The Topoisomerase 1 Inhibitor Austrobailignan-1 Isolated from Koelreuteria henryi Induces a G2/M-Phase Arrest and Cell Death Independently of p53 in Non-Small Cell Lung Cancer Cells |
| Authors: | Wu, Chun-Chi
Huang, Keh-Feng
Yang, Tsung-Ying
Li, Ya-Ling
Wen, Chi-Luan
Hsu, Shih-Lan
Chen, Tzu-Hsiu |
| Contributors: | 保健營養系 |
| Keywords: | Cyclearrest
Induced apoptosis
Dna-damage
A549 cells
Carcinoma
Pathways
Activation
Irinotecan
Cisplatin
Protein |
| Date: | 2015-07 |
| Issue Date: | 2016-04-19 19:06:05 (UTC+8) |
| Publisher: | Public Library Science |
| Abstract: | Koelreuteria henryi Dummer, an endemic plant of Taiwan, has been used as a folk medicine for the treatment of hepatitis, enteritis, cough, pharyngitis, allergy, hypertension, hyperlipidemia, and cancer. Austrobailignan-1, a natural lignan derivative isolated from Koelreuteria henryi Dummer, has anti-oxidative and anti-cancer properties. However, the effects of austrobailignan-1 on human cancer cells have not been studied yet. Here, we showed that austrobailignan-1 inhibited cell growth of human non-small cell lung cancer A549 and H1299 cell lines in both dose- and time-dependent manners, the IC50 value (48 h) of austrobailignan-1 were 41 and 22 nM, respectively. Data from flow cytometric analysis indicated that treatment with austrobailignan-1 for 24 h retarded the cell cycle at the G2/M phase. The molecular event of austrobailignan-1-mediated G2/M phase arrest was associated with the increase of p21(Waf1/Cip1) and p27(Kip1) expression, and decrease of Cdc25C expression. Moreover, treatment with 100 nM austrobailignan-1 for 48 h resulted in a pronounced release of cytochrome c followed by the activation of caspase-2, -3, and -9, and consequently induced apoptosis. These events were accompanied by the increase of PUMA and Bax, and the decrease of Mcl-1 and Bcl-2. Furthermore, our study also showed that austrobailignan-1 was a topoisomerase 1 inhibitor, as evidenced by a relaxation assay and induction of a DNA damage response signaling pathway, including ATM, and Chk1, Chk2,YH2AX phosphorylated activation. Overall, our results suggest that austrobailignan-1 is a novel DNA damaging agent and displays a topoisomerase I inhibitory activity, causes DNA strand breaks, and consequently induces DNA damage response signaling for cell cycle G2/M arrest and apoptosis in a p53 independent manner. |
| Relation: | Plos One, v.10 n.7,Article ID e0132052 |
| Appears in Collections: | [Dept. of Health and Nutrition (including master's program)] Periodical Articles
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