| Anticancer activity of isoobtusilactone A from Cinnamomum kotoense: involvement of apoptosis, cell-cycle dysregulation, mitochondria regulation, and reactive oxygen species. | |
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MedLine Citation:
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PMID: 18489163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, we investigate the anticancer effect of isoobtusilactone A (IOA), a constituent isolated from the leaves of Cinnamomum kotoense, on human non-small cell lung cancer (NSCLC) A549 cells. IOA was found to induce the arrest of G2-M phase, induce apoptosis, increase sub-G1, and inhibit the growth of these cells. Further investigation revealed that IOA's blockade of the cell cycle was associated with increased levels of p21/WAF1, p27 (kip1), and p53. In addition, IOA triggered the mitochondrial apoptotic pathway, as indicated by an increase in Bax/Bcl-2 ratios, resulting in a loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. We also found the generation of reactive oxygen species (ROS) to be a critical mediator in IOA-induced inhibition of A549 cell growth. In antioxidant and NO inhibitor studies, we found that by pretreating A549 cells with either N-acetylcystenine (NAC), catalase, mannitol, dexamethasone, trolox, or L-NAME we could significantly decrease IOA production of ROS. Moreover, using NAC to block ROS, we could significantly suppress IOA-induced antiproliferation, antimigration, and anti-invasion. Finally, we found that IOA inhibited the migration and invasion of A549 cell migration and invasion. Taken together, these results suggest that IOA has anticancer effects on A549 cells. |
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Authors:
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Chung-Yi Chen; Ching-Hsein Chen; Yi-Ching Lo; Bin-Nan Wu; Hui-Min Wang; Wen-Li Lo; Chuan-Min Yen; Rong-Jyh Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-05-20 |
Journal Detail:
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Title: Journal of natural products Volume: 71 ISSN: 1520-6025 ISO Abbreviation: J. Nat. Prod. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-27 Completed Date: 2008-09-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906882 Medline TA: J Nat Prod Country: United States |
Other Details:
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Languages: eng Pagination: 933-40 Citation Subset: IM |
Affiliation:
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School of Medicine and Health Sciences, Fooyin UniVersity, Kaohsiung County 831, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkanes
/
chemistry,
isolation & purification*,
pharmacology* Antineoplastic Agents, Phytogenic / chemistry, isolation & purification*, pharmacology* Apoptosis / drug effects* Caspase 3 / analysis, metabolism Caspase 9 / analysis, metabolism Cell Cycle / drug effects* Cinnamomum / chemistry* Cyclin-Dependent Kinase Inhibitor p21 / analysis, metabolism Cytochromes c / analysis, metabolism Drug Screening Assays, Antitumor Humans Lactones / chemistry, isolation & purification*, pharmacology* Mitochondria / drug effects* Plant Leaves / chemistry Plants, Medicinal / chemistry* Proto-Oncogene Proteins c-bcl-2 / analysis, metabolism Reactive Oxygen Species / chemistry Taiwan Tumor Suppressor Protein p53 / analysis, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Alkanes; 0/Antineoplastic Agents, Phytogenic; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Lactones; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 0/isoobtusilactone A; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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