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.
7. Prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer
Prostacyclin synthase and thromboxane
synthase signaling via arachidonic acid metabolism affects a number of
tumor cell survival pathways such as cell proliferation, apoptosis,
tumor cell invasion and metastasis, and angiogenesis. While prostacyclin
synthase is generally believed to be anti-tumor, a pro-carcinogenic
role for thromboxane synthase has been
demonstrated in a variety of cancers. According to the study by the St.
James's Hospital, the expression and activity of this enzyme may protect
against tumor development. In this review, we discuss the aberrant
expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. The
study also discusses the effects of these enzymes on a range of tumor
cell survival pathways, such as tumor cell proliferation, induction of
apoptosis, invasion and metastasis, and tumor cell angiogenesis. As
downstream signaling pathways of these enzymes have also been implicated
in cancer states, we examine the role of
downstream effectors of PGIS and TXS activity in tumor growth and
progression. Finally, the current therapeutic strategies aimed at
targeting these enzymes for the prevention/treatment of cancer(7).
8. Increased cyclooxygenase-2 and thromboxane synthase expression in human erythroleukemia cells
Diosgenin is a very interesting natural product
because, depending on the specific dose used, its biological effect is
very different in HEL (human erythroleukemia) cells. For example, at 10
microM, diosgenin induced megakaryocytic differentiation, in contrast to
40 microM diosgenin, which induced apoptosis in HEL cells previously
demonstrated using sedimentation field-flow fractionation (SdFFF). In
the study by the Université de Limoges, indicated that the implication
of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in
HEL cells. Furthermore, we showed that the analytical technique of SdFFF
may be used as a tool to confirm our results as a function of the
degree of cell differentiation(8).
9. Cyclooxygenase-2 and thromboxane synthase in non-endocrine and endocrine tumors
Prostaglandins (PG) are
members of a large group of hormonally active fatty acids derived from
free fatty acids. They are formed from arachidonic acid-the major PG
precursor. Cyclooxygenase (COX)-1 and -2 are the rate-limiting steps in
PG synthesis. COX-2 is overexpressed in many human non-endocrine and
endocrine tumors including colon, breast, prostate, brain, thyroid, and
pituitary. According to the study by the Mayo Clinic College of
Medicine, Thromboxane synthase (TS) catalyzes the synthesis of thromboxane
A2 (TXA2), which is derived from arachidonic acid and prostaglandin H2
and is a vasoconstrictor and inducer of platelet aggregation. TXA2
stimulates tumor growth and spread of some tumors and TS appears to have
a critical role in tumorigenesis in some organ systems. The
accumulating evidence points to an increasingly important role of COX-2
and TS in tumor progression and metastasis(9).
10. Activation of the thromboxane A2 pathway in human prostate cancer correlates
In the study to investigate the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer
(PCa) by analyzing the expression of cyclooxygenase-2 (COX-2), TXA(2)
synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the
TXA(2) pathway, was analyzed on serial tissue sections from 46 human PCa
specimens, found that Proteins specifically involved in the TXA(2)
pathway are up-regulated in human PCa and their level of expression is
associated with tumor extraprostatic extension and loss of
differentiation. The study is the first to examine simultaneously all
key proteins involved in this pathway including TXA(2) receptors and
results suggest that the TXA(2) pathway may be a potential target for
PCa prevention/therapy(10).
11. Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer
Thromboxane synthase (TxS) metabolizes the cyclooxygenase product, prostaglandin H(2), into thromboxanes. Some of the thromboxanes are known to be biologically active on cancer cells. In the study to investigate the expression of thromboxane synthases, TBXAS1 and the thromboxane A2 receptor, TBXA2R in a cohort of human breast cancer patients and also to assess their potential clinical relevance, showed that thromboxane synthases are differentially expressed in human breast cancer.
While TBXA2R is highly expressed in aggressive tumours and linked with
poor prognosis, TBXAS1 is expressed at significantly low levels in high
grade tumours and tumour patients with poor prognosis. TBXA2R thus has a
significant prognostic value in clinical breast cancer(11).
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Sources
(7) http://www.ncbi.nlm.nih.gov/pubmed/20122998
(8( http://www.ncbi.nlm.nih.gov/pubmed/18549804
(9) http://www.ncbi.nlm.nih.gov/pubmed/16627914
(10) http://www.ncbi.nlm.nih.gov/pubmed/16522350
(11) http://www.ncbi.nlm.nih.gov/pubmed/16250911
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