Thromboxane
Thromboxane is memeber of member of the family of lipids known as
eicosanoids, containing 2 major thromboxanes, Thromboxane A2, a potent
stimulator of platelet aggregation, and thromboxane B2, a metabolite of
thromboxane A2 which is known to be highly unstable under physiological conditions.
1. The thromboxane synthase and receptor signaling pathway in cancer
Thromboxane A(2) (TXA(2)) is a biologically active metabolite of arachidonic acid formed by the action of the terminal synthase, thromboxane
A(2) synthase (TXA(2)S), on prostaglandin endoperoxide (PGH(2)). TXA(2)
is responsible for multiple biological processes through its cell
surface receptor, the T-prostanoid (TP) receptor. According to the study
by the Wayne State University, potential involvement of TXA(2)S and TP
in tumor progression, especially tumor cell proliferation, migration,
and invasion that are key steps in cancer
progression. In addition, the regulation of neovascularization by TP
has been identified as a potent source of control during oncogenesis(1).
2. Pesveratrol to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes
Platelet aggregation around migrating cancer
cells protects them against the activity of natural killer cells
(NKCs). The inability of immune system to response results in the
progression of malignant diseases. In the study to evaluate the effects
of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and
NKCs activity and the platelet aggregation, production of thromboxane
B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa
(major biological markers for platelet aggregation) and functional
activity of the NKCs against the K562 cancer
cell line after incubation with various concentrations of reveratrol,
found that resveratrol can be used as an additional supplement to
modulate the immune system and to inhibit platelet aggregation in
thromboembolic episodes. Further clinical investigation in vivo could
lead to specific concentrations that may maximize the beneficial effect
of resveratrol(2).
3. Thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform and Bladder cancer
Increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform are found in the tissues of patients with bladder cancer. In the study by the University of South Carolina to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients, found that increased levels of thromboxane
B(2) (TXB(2)) the major metabolite of TXAS and increased levels of the
TPβ receptor. These results raised the possibility that patients with
bladder cancer may be followed for progression or remission of their disease by quantitation of these substances in their urine(3).
4. Thromboxane synthase and Non small cell cancer
Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer
cells. TXS over-expression has been reported in a range of cancers, and
associated with a poor prognosis. In the study toexamine the TXS
expression in human NSCLC and matched controls by western analysis and
IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient
NSCLC TMA was stained for COX-2 and downstream TXS expression, indicated
that TXS is over-expressed in NSCLC, particularly in the adenocarcinoma
subtype. Inhibition of this enzyme inhibits proliferation and induces
apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC(4).
5. Endogenous levels of AA and selected eicosanoids and colon cancer
Cumulative evidence shows that eicosanoids such as prostaglandins, leukotrienes, thromboxanes and hydroxy eicosatetraenoic acids play an important role in associating inflammation with human colorectal cancer
(CRC). In the study In the study of an ultra-pressure liquid
chromatography/tandem mass spectrometry (UPLC/MS/MS) method was
developed and validated for the targeted profiling of eight relevant
eicosanoids and the major metabolic precursor, arachidonic acid (AA), in
human colon, applied for the clinical profiling of matched pairs of
cancerous and normal colon mucosae obtained from eight colorectal cancer
patients, indicated that Endogenous levels of AA and selected
eicosanoids such as prostaglandin E(2) (PGE(2)), prostacyclin (PGI(2))
[assayed as its stable hydrolytic product 6-keto-prostaglandin(1α) (6-k
PGF(1α))] and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE)
were found to be significantly different (p <0.05; paired t-test)
between cancerous and normal mucosae(5).
6. The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer
The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer
is poorly understood. In the study to examine the role of TxA(2) in
smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK)-promoted cell survival and growth in human lung cancer cells, found that NNK stimulates TxA(2) synthesis and activates its receptor in lung cancer
cells. The increased TxA(2) may then activate CREB through PI3K/Akt and
extracellular ERK pathways, thereby contributing to the NNK-promoted
survival and growth of lung cancer cells(6).
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22037941
(2) http://www.ncbi.nlm.nih.gov/pubmed/23617069
(3) http://www.ncbi.nlm.nih.gov/pubmed/21983220
(4) http://www.ncbi.nlm.nih.gov/pubmed/21388528
(5) http://www.ncbi.nlm.nih.gov/pubmed/21337637
(6) http://www.ncbi.nlm.nih.gov/pubmed/20818420
Health Researcher and Article Writer. Expert in Health Benefits of Foods, Herbs, and Phytochemicals. Master in Mathematics & Nutrition and BA in World Literature and Literary criticism. All articles written by Kyle J. Norton are for information & education only.
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