| Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production. | |
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MedLine Citation:
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PMID: 20620131 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Overexpression of c-Myc represents the most frequently deregulated genetic event in cancer, and therefore c-Myc may represent a good molecular target for cancer therapy. The human lung carcinoma cell line, NCI-H1299, shows resistance to conventional cancer treatments, such as ionizing radiation (IR) and cisplatin, while the lung carcinoma cell line, NCI-H460, is sensitive to treatment with these agents. However, when treated with a chalcone compound [toluenesulfonylamido-chalcone, 4'-(p-toluene sulfonyl amino)-3,4-dihydroxy chalcone (TSHDC)], cell death was dramatically induced in NCI-H1299 cells as compared to NCI-H460 cells. TSHDC-mediated cytotoxicity was not dependent on the status of p53 and p21. However, TSHDC exerted increased c-Myc-dependent reactive oxygen species (ROS) production in NCI-H1299 cells in which c-Myc is overexpressed, while increased ROS production did not occur in A549 or NCI-H460 cells with a low c-Myc level. Several colon and brain cancer cells also showed a correlation between c-Myc expression and TSHDC-mediated increased cell death. Tumor regression by TSHDC was more dramatic in NCI-H1299 cells than NCI-H460 cells, when these cells were grafted to nude mice. However, in the case of IR and cisplatin, NCI-H460 cells were more sensitive than NCI-H1299 cells. From these results, c-Myc-mediated ROS production may be a good target for screening of novel cancer drugs and TSHDC might be a good candidate as a cancer drug, specifically in cancer cells that overexpress c-Myc. |
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Authors:
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Tae-Hee Kim; Woo Duck Seo; Hyung Won Ryu; Haeng Ran Seo; Yeung Bae Jin; Minyoung Lee; Young-Hoon Ji; Ki Hun Park; Yun-Sil Lee |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-08 |
Journal Detail:
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Title: Chemico-biological interactions Volume: 188 ISSN: 1872-7786 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-10-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
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Languages: eng Pagination: 111-8 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology* Blotting, Western Cell Line, Tumor Chalcones / pharmacology* Flow Cytometry Humans Mice Mice, Nude Neoplasm Transplantation Proto-Oncogene Proteins c-myc / metabolism* Reactive Oxygen Species / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Chalcones; 0/Proto-Oncogene Proteins c-myc; 0/Reactive Oxygen Species |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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