Document Detail


Identification of small molecule inhibitors of telomerase activity through transcriptional regulation of hTERT and calcium induction pathway in human lung adenocarcinoma A549 cells.
MedLine Citation:
PMID:  20813535     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug or dietary food components is a new strategy for cancer prevention. In this report, we examined the effects of fourteen natural or synthetic compounds on TA in human lung adenocarcinoma A549 cells. The results demonstrated that some of the tested compounds inhibited TA, being 2'-hydroxy-2,3,4',6'-tetramethoxychalcone (HTMC) was the most potent among tested. In A549 cells, HTMC also inhibited the cell proliferation, decreased the expression of human telomerase reverse transcriptase (hTERT) and sequentially reduced the hTERT promoter. In soft agar assay HTMC treatment reduced the colony formation of A549 cells. Cellular fractionation and immunofluorescence assay demonstrated that there was no translocation of hTERT from nuclei to cytoplasm. Further studies revealed that the release of Ca(2+) was the underlying mechanism of suppressed TA and hTERT transcription in A549 cells exposed to HTMC. These in vitro data support the development of HTMC as a therapeutic agent for cancer complications.
Authors:
Yerra Koteswara Rao; Te-Yu Kao; Ming-Fang Wu; Jiunn-Liang Ko; Yew-Min Tzeng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-13
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6987-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Wufeng, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / enzymology,  metabolism*
Antineoplastic Agents / chemical synthesis,  chemistry,  pharmacology*
Calcium / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis,  chemistry,  pharmacology*
Humans
Lung Neoplasms / enzymology,  metabolism*
Molecular Structure
Molecular Weight
Promoter Regions, Genetic / drug effects,  genetics
Structure-Activity Relationship
Telomerase / antagonists & inhibitors*,  genetics,  metabolism
Transcription, Genetic / drug effects*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 7440-70-2/Calcium; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

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