Document Detail

Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production.
MedLine Citation:
PMID:  20620131     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-08
Journal Detail:
Title:  Chemico-biological interactions     Volume:  188     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  111-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Republic of Korea.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Blotting, Western
Cell Line, Tumor
Chalcones / pharmacology*
Flow Cytometry
Mice, Nude
Neoplasm Transplantation
Proto-Oncogene Proteins c-myc / metabolism*
Reactive Oxygen Species / metabolism*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Chalcones; 0/Proto-Oncogene Proteins c-myc; 0/Reactive Oxygen Species

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