The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells

doi:10.1016/0145-2126(94)90079-5

Leukemia Research

Volume 18, Issue 6, June 1994, Pages 431-439

https://doi.org/10.1016/0145-2126(94)90079-5 Get rights and content

Abstract

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G₂/M arrest at low genistein concentrations (5–10 μg/ml), while at higher doses (20–30 μg/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptosic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 μ/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy.

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Original articleThe natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells

Abstract

Growth factors in development, transformation and tumorigenesis

Cell

Growth factor receptors tyrosine kinases

A. Rev. Biochem.

Oncogenes and signal transduction

Cell

Signal transduction by receptors with tyrosine kinase activity

Cell

Signal transduction inhibitors as novel anticancer drugs: where are we?

Ann. Oncol.

A specific inhibitor for tyrosine protein kinase from Pseudomonas

J. Antibiot. (Tokyo)

Genistein, a specific inhibitor of tyrosine-specific protein kinases

J. biol. Chem.

Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming traditional Japanese diet

Am. J. clin. Nutr.

Plasma concentrations of phyto-estrogens in Japanese men

Lancet

Non-steroidal estrogen of dietary origin: possible roles in hormone-dependent disease

Am. J. clin. Nutr.

Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene

Biochem. biophys. Res. Commun.

Identification in human urine of a natural growth inhibitor for cells derived from solid paediatric tumours

Eur. J. Clin. Invest.

Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction

Rapid hypotonic method for flow cytofluorometry of monolayer cell cultures

Inhibition of human breast cancer cell (MCF-7) growth in vitro by the somatostatin analog SMS 201–995: effects on cell cycle parameters and apoptotic cell death

Endocrinology

A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry

J. Immun. Methods

Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine

Genistein inhibits tumor cell growth in vitro but enhances mitochondrial reduction of tetrazolium salts: a further pittfall in the use of the MTT assay for evaluating cell growth and survival

Eur. J. Cancer

Putting it on and taking it off: phosphoprotein phosphatase involvement in cell cycle regulation

Cell

The cell cycle as a cdc2 cycle

Nature

Creative blocks: cell-cycle checkpoints and feedback controls

Nature

Original article
The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells