Genistein Induces G2 Arrest in Malignant B Cells by Decreasing IL-10 Secretion

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 demonstrated that the soy isoflavone genistein, a tyrosin...

Full description

Saved in:
Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2004-12, Vol.3 (12), p.1597-1605
Main Authors: Mansour, Amal, McCarthy, Brian, Schwander, Stephan K, Chang, Victor, Kotenko, Sergei, Donepudi, Sreekrishna, Lee, Janet, Raveche, Elizabeth
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Apoptosis Regulatory Proteins - metabolism
B-Lymphocytes - drug effects
B-Lymphocytes - pathology
B-Lymphocytes - secretion
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Cycle Proteins - metabolism
Cell Proliferation - drug effects
Cycle
Cytotoxicity, Immunologic
Dose-Response Relationship, Drug
Flow Cytometry
G2 Phase - drug effects
Genistein - pharmacology
Humans
Interferon-gamma - biosynthesis
Interferon-gamma - metabolism
Interleukin-10 - genetics
Interleukin-10 - metabolism
Interleukin-10 - secretion
Landes
Organogenesis
Proteins
Receptors, Interleukin - metabolism
Receptors, Interleukin-10
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tumor Cells, Cultured
Vidarabine - analogs & derivatives
Vidarabine - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 demonstrated that the soy isoflavone genistein, a tyrosine kinase inhibitor, rapidly decreased IL-10 secretion followed by upregulation of IFN-gamma and inhibition of cell proliferation with predominantly G2 arrest. The antiproliferative effects of genistein could be 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 re-entered 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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.3.12.1293