10th April 07:55
inhibitors of Nuclear factor kappa-B (aspirin stress virus colon cancer)
As I said in a previous post, Nuclear Factor Kappa B (NF-kappaB) is like the
granddaddy of cancer genetic triggers, at least in panc cancer and possibly
breast and colon cancers, triggering a lot of the genes that make cancer
cells resistant to chemo, that cause angiogenesis (new blood vessel
formation), and metastases. One of the most troublesome genes it triggers
is Bcl-xL which itself triggers another bunch of troublesome genes.
(I had thought NF-kappaB was a gene but this is not true as the abstract
below points out),
Below is a good explanation of how NF-kappaB works and what inhibits it.
It's starting to appear that protease inhibitors, N-Acetyl-L-cysteine (NAC),
alpha-Lipoic acid and other substances may be effective in inhibiting some
cancers (all those that use NF-kappaB).
Curr Med Chem. 2003 Aug;10(16):1603-15.
Nuclear factor kappa B: a potential target for anti-HIV chemotherapy.
Pande V, Ramos MJ.
CEQUP/Departamento de Quimica, Faculdade de Ciencias, Universidade do Porto,
Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
The Nuclear Factor Kappa B (NF-kappaB) is a lymphoid-specific transcription
factor, which is sequestered in the cytoplasm by the protein IkappaB.
NF-kappaB plays a major role in the regulation of HIV-1 gene expression.
Upon activation, NF-kappaB is released from IkappaB, moves to the nucleus,
and binds to its sites on the HIV long terminal repeat to start
transcription of integrated HIV genome. The present review focuses on the
NF-kappaB as a potential target for the development of chemotherapy against
HIV-1. Beginning from the viral-binding to reverse transcription,
integration, and gene expression, to the virion maturation, the life cycle
of HIV presents drug-targets at all the stages. As a result, many drugs have
been developed and have entered clinical trials. Some of the most important
of these are reverse transcriptase and protease inhibitors, which have been
used mostly in clinical studies in the form of combined therapy. But, this
combined therapy has presented the problem of resistance, due to mutations
in the virus. However, targeting NF-kappaB for the suppression of virus does
not present the problem of resistance, as NF-kappaB is a normal part of the
human T-4 cell, and is not subject to mutations, as is the virus. An
overview of the NF-kappaB system and its role in HIV-1 is presented,
followed by a critical review of its current and potential synthetic
inhibitors. The drugs studied against NF-kappaB fall mainly into three
categories: (1) Antioxidants, against oxidative stress conditions, which aid
in NF-kappaB activation, (2) IkappaB phosphorylation and degradation
inhibitors (the phosphorylation and degradation of IkappaB is necessary to
make NF-kappaB free and move to the nucleus), and (3) NF-kappaB DNA binding
inhibitors. The antioxidants include N-Acetyl-L-cysteine (NAC), alpha-Lipoic
acid, glutathione monoester, pyrrolidine dithiocarbamate, and tepoxalin, of
which NAC is the best studied. The IkappaB phosphorylation and degradation
inhibitors, which have been studied in the context of HIV-1 include the
salicylates (sodium salicylate, and acetylsalicylic acid (aspirin)).
Finally, the NF-kappaB DNA binding inhibitors, which have received attention
only recently, are reviewed. These include the most potential, aurine
tricarboxylic acid (ATA), a chelating agent, which has been found to inhibit
NF-kappaB DNA binding at a low concentration of 30 micro M. The probable
mechanism of action of these drugs is discussed alongwith relevant
suggestions and conclusions.
10th April 07:57
inhibitors of Nuclear factor kappa-B (aspirin)
These include the most potential, aurine
tricarboxylic acid (ATA), a chelating agent,
Seeing aspirin has been shown to bind iron .. I wonder about the above ..
Who loves ya.
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13th April 04:21
inhibitors of Nuclear factor kappa-B (tumor carcinogenesis)
Correct. That I am talking about the mutated version of p53 is generally
assumed in the context. Defects in p53 function are far more central to
carcinogenesis than NF-kB activation. p53 mutations are found in high
percentages of certain cancers, as high as 90% in some tumor types. They
don't call p53 the "guardian of the genome" for nothing.
Other mutations (K-ras, for instance) are more prevalent in other tumor
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