Document Detail


Genistein induces G2 arrest in malignant B cells by decreasing IL-10 secretion.
MedLine Citation:
PMID:  15611648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic B cell malignancies are often chemoresistant and the development of new therapeutic modalities is a high priority. Many B cell malignancies have autocrine production of IL-10, which regulates B cell growth and differentiation. Here we demonstrate that the soy isoflavone genistein, a tyrosine kinase inhibitor, rapidly decreased IL-10 secretion followed by upregulation of IFNgamma and inhibition of cell proliferation with pre-dominantly G2 arrest. The antiproliferative effects of genistein were reversed by the addition of exogenous IL-10. Genistein downregulated cdc25C and cdk1 as well as anti-apoptotic proteins survivin and Ian-5. After genistein withdrawal, the G2M arrested cells reentered the cell cycle and underwent apoptosis, which was significantly augmented by fludarabine. We conclude that genistein can sensitize malignant B cells to the action of other chemotherapeutic agents by modulating the cytokine profile and controlling cell cycle progression.
Authors:
Amal Mansour; Brian McCarthy; Stephan K Schwander; Victor Chang; Sergei Kotenko; Sreekrishna Donepudi; Janet Lee; Elizabeth Raveche
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Publication Detail:
Type:  Journal Article     Date:  2004-12-08
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  3     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2005-02-01     Completed Date:  2006-04-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1597-605     Citation Subset:  IM    
Affiliation:
New Jersey Medical School, UMDNJ, Newark, New Jersey 07103, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
B-Lymphocytes / drug effects*,  pathology*,  secretion
Cell Cycle Proteins / metabolism
Cell Proliferation / drug effects
Cytotoxicity, Immunologic
Dose-Response Relationship, Drug
Flow Cytometry
G2 Phase / drug effects*
Genistein / pharmacology*
Humans
Interferon-gamma / biosynthesis,  metabolism
Interleukin-10 / genetics,  metabolism,  secretion*
RNA, Messenger / genetics,  metabolism
Receptors, Interleukin / metabolism
Receptors, Interleukin-10
Tumor Cells, Cultured
Vidarabine / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Cell Cycle Proteins; 0/RNA, Messenger; 0/Receptors, Interleukin; 0/Receptors, Interleukin-10; 130068-27-8/Interleukin-10; 21679-14-1/fludarabine; 446-72-0/Genistein; 5536-17-4/Vidarabine; 82115-62-6/Interferon-gamma

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


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