| Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor. | |
| | |
MedLine Citation:
|
PMID: 15131795 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND & AIMS: Barrett's esophageal adenocarcinoma (BEAC) is a complication of gastroesophageal reflux disease, with no effective chemotherapy and poor prognosis. BEAC cells, like many other types of cancers, may reactivate telomerase to achieve unlimited proliferative potential, making telomerase a unique therapeutic target. The purpose of this study was to evaluate effects of telomerase inhibition on BEAC. METHODS: We examined the effect of a selective G-quadruplex intercalating telomerase inhibitor, 2,6-bis[3-(N-Piperidino)propionamido]anthracene-9,10-dione (PPA), on telomerase activity, telomere length, colony size distribution, and proliferative potential in 2 BEAC cell lines, BIC-1 and SEG-1. RESULTS: Telomerase activity was >10-fold and >600-fold elevated in the adenocarcinoma cells as compared with normal gastric/intestinal cells and normal diploid fibroblasts, respectively. Telomeres were short, being less than 4 kilobase pair in both tumor cell lines. Exposure to PPA effectively inhibited telomerase activity and shortened telomeres. PPA also arrested cell proliferation and reduced colony number and size after a lag period of about 10 cell generations, consistent with the attrition of telomeres. The growth arrest was not due to senescence but was due to apoptosis. Expression analysis of the cells following PPA treatment did not show significant change in the expression of genes involved in cell-cycle proliferation and apoptosis. Exposure to PPA had no effect on proliferative potential of normal intestinal cells. CONCLUSIONS: We conclude that telomerase inhibition by PPA induces cell growth arrest in BEAC cells and demonstrate the potential of telomerase inhibitors in chemoprevention and treatment of Barrett's-associated esophageal adenocarcinoma. |
| | |
Authors:
|
Masood A Shammas; Hemanta Koley; David G Beer; Cheng Li; Raj K Goyal; Nikhil C Munshi |
Related Documents
:
|
9737385 - Chromosomal characterization of mrc-5 cell banks utilizing g-banding technique. 21726505 - Prolactin-cell adenoma with signet-ring cells: a case report. 22113335 - Three-dimensional studies of prop1-expressing cells in the rat pituitary primordium of ... 3944195 - Gangliosides stimulate astroglial cell proliferation in the absence of serum. 8224515 - Differentiation and uteroglobin gene expression by novel rabbit endometrial cell lines. 22172325 - Induction of apoptosis in human hepatoma smmc-7721 cells by solamargine from solanum ni... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Gastroenterology Volume: 126 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 2004 May |
Date Detail:
|
Created Date: 2004-05-07 Completed Date: 2004-06-23 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
|
Languages: eng Pagination: 1337-46 Citation Subset: AIM; IM |
Affiliation:
|
VA Boston Health Care System, Boston, MA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenocarcinoma
/
etiology,
pathology,
physiopathology* Anthraquinones / pharmacology* Apoptosis* / drug effects Barrett Esophagus / complications* Cell Division / drug effects Cell Line, Tumor Enzyme Inhibitors / pharmacology* Esophageal Neoplasms / etiology, pathology, physiopathology* Gene Expression / drug effects Gene Expression Profiling Humans Piperidines / pharmacology* Stem Cells / pathology Telomerase / antagonists & inhibitors*, metabolism Telomere / drug effects, genetics* |
| Grant Support | |
ID/Acronym/Agency:
|
DK 031092/DK/NIDDK NIH HHS; P01 78378//PHS HHS; P50 CA 10070/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/2,6-bis(3-(N-piperidino)propionamido)anthracene-9,10-dione; 0/Anthraquinones; 0/Enzyme Inhibitors; 0/Piperidines; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.
Next Document: The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells.