Document Detail


Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: suppression of telomerase activity by LAPA.
MedLine Citation:
PMID:  20438329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Up-regulation of telomerase activity is associated with immortalization and unlimited cell division in most cancer cells. Therefore, telomerase represents a particularly attractive target for anticancer therapy. Recent reports have suggested that beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of tumor cells. However, the underlying relationship between telomerase activity and apoptosis in response to LAPA exposure in leukemia cells remains poorly understood. In this study, we confirmed that LAPA treatment induces direct cytotoxicity in human leukemia cells (U937, K562, HL60, and THP-1) through activation of caspase-3 and subsequent cleavage of poly(ADP-ribose) polymerase. The observed induction of cell death was associated with decreased telomerase activity, which was ascribed to down-regulation of telomerase reverse transcriptase. Additionally, overexpression of anti-apoptotic Bcl-2 could not overcome the induction of apoptosis or the decreased telomerase activity in response to treatment of U937 cells with LAPA. We conclude that LAPA has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.
Authors:
Dong-Oh Moon; Chang-Hee Kang; Mun-Ock Kim; You-Jin Jeon; Jae-Dong Lee; Yung Hyun Choi; Gi-Young Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal food     Volume:  13     ISSN:  1557-7600     ISO Abbreviation:  J Med Food     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-04     Completed Date:  2010-08-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9812512     Medline TA:  J Med Food     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-8     Citation Subset:  IM    
Affiliation:
Department of Marine Sciences, Jeju National University, Jeju, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Caspase 3 / metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Down-Regulation*
HL-60 Cells
Humans
K562 Cells
Leukemia / drug therapy,  enzymology*,  physiopathology*
Naphthoquinones / pharmacology*
Plant Extracts / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Tabebuia / chemistry
Telomerase / metabolism*
U937 Cells
Chemical
Reg. No./Substance:
0/Naphthoquinones; 0/Plant Extracts; 4707-32-8/beta-lapachone; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.7.49/Telomerase; EC 3.4.22.-/Caspase 3

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