| DHF-18, a new synthetic flavonoid, induced a mitochondrial-mediated apoptosis of hepatocarcinoma cells in vivo and in vitro. | |
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MedLine Citation:
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PMID: 21093431 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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A new synthetic flavonoid DHF-18, synthesized with a piperazine substitution, has been recently found to show potent anti-tumor activities both in vivo and in vitro. In this study, we demonstrated that DHF-18 significantly inhibited tumor growth in mice inoculated with Heps hepatoma cells without evident toxicity. After the treatment of 40mg/kg DHF-18, the inhibitory rate of tumor weight was 53.69%. To investigate whether apoptosis induction contributed to the anti-tumor effects of DHF-18, DAPI (diamidino-phenyl-indole) staining and Annexin V/PI (Propidium iodide) double staining were performed in our tests. The data showed that DHF-18 could induce the apoptosis cell death in HepG2 cells. Moreover, the apparent increase of intracellular reactive oxygen species levels and the reduction of mitochondria ΔΨm were both observed in HepG2 cells after DHF-18 treatment. Meanwhile, the transposition of apoptotic inducing factor (AIF) from mitochondria to nuclei, the release of cytochrome c from mitochondria and the activation of caspase-3, -9 were also detected, indicating that DHF-18 may induce apoptosis through a mitochondrial-mediated pathway. Additionally, DHF-18 decreased the expression of Bcl-2 protein, whereas the levels of Bax and Bak were found to increase after DHF-18 treatment. Moreover, the activation of caspase-8, the increase of TNF-R1 (Tumor necrosis factor receptor) and Bid were found. Taken together, our results suggested that DHF-18 may induce HeG2 cells apoptosis through a mitochondrial-dependent and independent pathway. |
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Authors:
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Lin-bo Zhang; Lei Qiang; Fei-hong Chen; Tian Wu; Jing-jing Rong; Qing Zhao; Mei-juan Zou; Zhen Yang; Qi-dong You; Zhi-yu Li; Yu-lin Wu; Qing-long Guo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-18 |
Journal Detail:
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Title: European journal of pharmacology Volume: 651 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 33-40 Citation Subset: IM |
Copyright Information:
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Copyright © 2010. Published by Elsevier B.V. |
Affiliation:
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Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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