Genistein abolishes nucleoside uptake by cardiac fibroblasts

Genistein, a soy isoflavone, is reported to exert significant beneficial action in several human disorders, which has generated immense interest in the mechanisms underlying its effects on diverse cellular processes. It has anti-proliferative action on many cell types, an effect generally attributed...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2009-12, Vol.332 (1-2), p.121-125
Main Authors: Pillai, Malini S, Shivakumar, K
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Cardiology
Cells, Cultured
Cellular biology
Fibroblasts - drug effects
Fibroblasts - metabolism
Genistein - pharmacology
Life Sciences
Male
Medical Biochemistry
Molecular biology
Myocardium - cytology
Nucleoside Transport Proteins - metabolism
Oncology
Phytoestrogens - pharmacology
Rats
Rats, Sprague-Dawley
Soy products
Thymidine - metabolism
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Summary:Genistein, a soy isoflavone, is reported to exert significant beneficial action in several human disorders, which has generated immense interest in the mechanisms underlying its effects on diverse cellular processes. It has anti-proliferative action on many cell types, an effect generally attributed to tyrosine kinase inhibition. In this study, genistein was found to cause total inhibition of [³H]-thymidine incorporation into DNA and a modest reduction in [³H]-proline incorporation into protein in primary cultures of cardiac fibroblasts. The decrease in [³H]-thymidine incorporation was not associated with a decrease in cell proliferation but correlated exactly with low intracellular levels of [³H]-thymidine. Genistein dramatically reduced [³H]-thymidine but not [³H]-proline uptake by these cells in which the equilibrative nucleoside transporter may be the major route of nucleoside uptake. The effect was irreversible and was demonstrable in pulmonary fibroblasts as well. The findings suggest that nucleoside uptake mechanisms may be a novel target of genistein action in cardiac fibroblasts and point to serious limitations in using genistein to assess the role of tyrosine kinase in cell proliferation by the standard technique of [³H]-thymidine incorporation.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-009-0181-7