Document Detail


Monensin-mediated growth inhibition in human lymphoma cells through cell cycle arrest and apoptosis.
MedLine Citation:
PMID:  12406077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monensin, a Na+ ionophore, regulates many cellular functions, including apoptosis. We investigated the in vitro antiproliferative effect of monensin on nine human lymphoma cell lines. Monensin significantly inhibited the proliferation of all the lymphoma cell lines examined with a 50% inhibition concentration of about 0.5 micromol/l, and induced a G1 and/or a G2-M phase arrest in these cell lines. To address the antiproliferative mechanism of monensin, we examined the effect of this drug on cell-cycle-related proteins in CA46 cells (both G1 and G2 arrest) and Molt-4 cells (G2 arrest). Treatment with monensin for 72 h decreased CDK4 and cyclin A levels in CA46 cells, and cdc2 levels in Molt-4 cells. In monensin-treated CA46 cells, increased p21-CDK2, p27-CDK2 and p27-CDK4 complex forms were observed. And, in monensin-treated Molt-4 cells, increased p21-cdc2 complex form was detected. Furthermore, the activities of CDK2- and CDK4-associated kinases were reduced in association with Rb hypophosphorylation in monensin-treated CA46 cells. The activity of cdc2-associated kinase was decreased in both cell lines, which was accompanied by induction of Wee1. Also, monensin induced apoptosis in these cell lines, as evidenced by annexin V binding assay and flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with loss of mitochondria transmembrane potential (Delta(psi)m). Taken together, these results demonstrated for the first time that monensin potently inhibits the proliferation of human lymphoma cell lines via cell cycle arrest and apoptosis.
Authors:
Woo Hyun Park; Jae Goo Seol; Eun Shil Kim; Won Ki Kang; Young Hyuck Im; Chul Won Jung; Byoung Kook Kim; Young Yiul Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  119     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-30     Completed Date:  2002-12-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  400-7     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, Seoul National University College of Medicine, Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Blotting, Western
CDC2-CDC28 Kinases
Cell Division / drug effects
Cyclin A / metabolism
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / metabolism
Cyclins / metabolism
Humans
Interphase
Ionophores / pharmacology*
Lymphoma / drug therapy
Membrane Potentials / drug effects
Monensin / pharmacology*
Tumor Cells, Cultured / drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin A; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Ionophores; 17090-79-8/Monensin; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cyclin-Dependent Kinases

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


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