Document Detail


Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition.
MedLine Citation:
PMID:  18358095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. METHODS: Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progression and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. RESULTS: Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the protein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. CONCLUSION: Rapamycin displayed a potent antileukemic effect in the human Tcell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.
Authors:
Yan-min Zhao; Qian Zhou; Yun Xu; Xiao-yu Lai; He Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  29     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-24     Completed Date:  2009-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  China    
Other Details:
Languages:  eng     Pagination:  481-8     Citation Subset:  IM    
Affiliation:
Bone Marrow Transplant Center, The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects*
Dose-Response Relationship, Drug
G1 Phase / drug effects
Humans
Jurkat Cells
Leukemia, T-Cell / drug therapy
RNA, Messenger / metabolism
Sirolimus / pharmacology*
Telomerase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/RNA, Messenger; 53123-88-9/Sirolimus; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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