ArticlePloS one2015
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.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 28 citations in OpenAlex.
- Structural basis for asymmetric bis-intercalator targeting of DNA triplex junctions enabling dual inhibition of topoisomerase I and oncogene transcription.Nucleic acids research · 2026Article
- Unified Asymmetric Synthesis of Aryltetralin Lactone Cyclolignans via Conformation-Assisted Radical C-H Cyclization.JACS Au · 2025Article
- LC-MS/MS-QTOF dataset of chemical compounds detected in honey samples from Bali and Lombok, Indonesia.Data in brief · 2024Article
- Attenuating role of withaferin A in the proliferation and migration of lung cancer cells via a p53-miR-27a/miR-10b pathway.Oncology letters · 2021Article
- Effect of timing of bisphosphonate administration on canine osteosarcoma cells undergoing radiation therapy.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2020Article
- Asymmetric Chemoenzymatic Synthesis of (-)-Podophyllotoxin and Related Aryltetralin Lignans.Angewandte Chemie (International ed. in English) · 2019Article
- CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer.Molecular medicine (Cambridge, Mass.) · 2019Article
- MHY440, a Novel Topoisomerase Ι Inhibitor, Induces Cell Cycle Arrest and Apoptosis via a ROS-Dependent DNA Damage Signaling Pathway in AGS Human Gastric Cancer Cells.Molecules (Basel, Switzerland) · 2018Article
- DNA damage-induced apoptosis and mitogen-activated protein kinase pathway contribute to the toxicity of dronedarone in hepatic cells.Environmental and molecular mutagenesis · 2018Article
- IMMUNEPOTENT CRP induces cell cycle arrest and caspase-independent regulated cell death in HeLa cells through reactive oxygen species production.BMC cancer · 2018Article
- Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway.Cancer management and research · 2018Article
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Authors and funding
7 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 p21Waf1/Cip1 and p27Kip1 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, γH2AX 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.
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