The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells.
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Istituti di Medicina Interna e Scienze Oncologiche, Università di Perugia, Italy.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 micrograms/ml), while at higher doses
(20-30 micrograms/ml) there was also a perturbation in S-phase
progression. The derangements in cell-cycle control were followed by
apoptotic death of genistein-treated cells. Immunocytochemical analysis
of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal
antibody showed that 30 micrograms/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.
Pharmacological studies have demonstrated that emodin when isolated from rhubarb exhibits anti-cancer effects on several human cancers, including human pancreatic cancer.[4][5][6] Emodin in rhubarb extracts may also have neuroprotective properties against glutamate toxicity,[7]
Aloe-emodin (1,3,8-trihydroxyanthraquinone) is a variety of emodin found in Socotrine, Barbados, and Zanzibar aloes, but not in Natal aloes.[citation needed]
Emodin is also shown to block cytomegalovirus infections as well as herpes simplex. Research is currently being performed in this area.
Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study.
Source
Institute of Life and Health Engineering, and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, China.Abstract
Genistein
exerts its anticarcinogenic effects by inducing G2/M arrest and
apoptosis of cancer cells. However, the precise molecular mechanism of
action of genistein has not been completely elucidated. In this study,
we used quantitative proteomics to identify the genistein-induced
protein alterations in gastric cancer cells and investigate the
molecular mechanism responsible for the anti-cancer actions of
genistein. Total 86 proteins were identified to be regulated by
genistein, most of which were clustered into the regulation of cell
division and G2/M transition, consistent with the anti-cancer effect of
genistein. Many proteins including kinesin family proteins, TPX2, CDCA8,
and CIT were identified for the first time to be regulated by
genistein. Interestingly, five kinesin family proteins including KIF11,
KIF20A, KIF22, KIF23, and CENPF were found to be simultaneously
downregulated by genistein. Significantly decreased KIF20A was selected
for further functional studies. The silencing of KIF20A inhibited cell
viability and induced G2/M arrest, similar to the effects of genistein
treatment in gastric cancer. And the silencing of KIF20A also increased
cancer cell sensitivity to genistein inhibition, whereas overexpression
of KIF20A markedly attenuated genistein-induced cell viability
inhibition and G2/M arrest. These observations suggested that KIF20A
played an important role in anti-cancer actions of genistein, and thus
may be a potential molecular target for drug intervention of gastric
cancer.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Sources of Genistein
Genistein is found in plant foods such as soybeans, chickpeas,
broccoli, cauliflower, alfalfa sprouts, clover sprouts, barley meal,
sunflower seeds, and clover seeds. It is also found in many soy-based
products such as soy milk, tempeh, miso, soy flour, infant formula,
sports drinks, protein bars, and textured soy protein. Textured soy
protein (TSP) is used as a meat substitute in vegetarian hamburgers, hot
dogs, sausages, and meatballs. Though soy is by far the most common
dietary source of genistein, it is not found in soy sauce or soybean
oil. Genistein is also available as a dietary supplement in powder,
pill, or capsule form.
Curcumin Inhibits Tyrosine Kinase Activity of p185neu and Also Depletes p185neu1
+ Author Affiliations
Abstract
Curcumin, a natural compound present in turmeric, possessing both anti-inflammatory and antioxidant effects, has been studied
vigorously as a chemopreventative in several cancer models. The erbB2/neu gene-encoded p185neu tyrosine kinase is a potent oncoprotein. Overexpression of p185neu in breast cancer is known to be a poor prognostic factor. We investigated the effect of curcumin on p185neu tyrosine kinase and on the growth of breast cancer cell lines. Curcumin dose-dependently inhibited p185neu autophosphorylation and transphosphorylation in vitro and depleted p185neu protein in vivo. It dissociated the binding of p185neu with GRP94 (glucose-regulated protein), a molecular chaperone, and enhanced the depletion of p185neu. The amount of p185neu
protein on the cell membrane was drastically decreased after curcumin
treatment. These data demonstrated a new mechanism
of the anti-tyrosine kinase activity of curcumin.
The growth of several breast cancer cell lines was inhibited; the IC50 ranged from 7 to 18 μm, which, however, did not correlate with the expression level of p185neu. Colony formation in the soft agar assay, a hallmark of the transformation phenotype, was preferentially suppressed in p185neu-overexpressing cell lines by 5 μm curcumin (% of control, basal level versus overexpression: 59.3 versus 16.7%; P < 0.001 by Student’s t test). Because curcumin effectively inhibited p185neu tyrosine kinase activity by depleting p185neu and potently suppressed the growth of multiple breast cancer cell lines, its therapeutic potential in advanced breast cancer
is worthy of further investigation.
Emodin, a Protein Tyrosine Kinase Inhibitor from Polygonum cuspidatum
Emodin is being studied as a potential agent that could reduce the impact of type 2 diabetes. It is a potent selective inhibitor of the enzyme 11β-HSD1.[2] In studies in obese mice, emodin limits the effect of glucocorticoids and may therefore ameliorate diabetes and insulin resistance.[3]
Pharmacological studies have demonstrated that emodin when isolated from rhubarb exhibits anti-cancer effects on several human cancers, including human pancreatic cancer.[4][5][6] Emodin in rhubarb extracts may also have neuroprotective properties against glutamate toxicity,[7]
Aloe-emodin (1,3,8-trihydroxyanthraquinone) is a variety of emodin found in Socotrine, Barbados, and Zanzibar aloes, but not in Natal aloes.[citation needed]
Emodin is also shown to block cytomegalovirus infections as well as herpes simplex. Research is currently being performed in this area.
List of plants that contain the chemical
- Senna obtusifolia[8] (syn. Cassia obtusifolia[9])
- Fallopia japonica[10] (syn. Polygonum cuspidatum[11])
- Ventilago madraspatana[12]
- Kalimeris indica[13]
- Rumex nepalensis[14]
- Polygonum hypoleucum[15]
- Cassia occidentalis[16]
- Cassia siamea[17]
- Acalypha australis[18]
- Rheum palmatum[19]
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