Antioxidants and NF-kB Activation
oxygen species (ROS) have the potential to induce indiscriminate damage to all biological
molecules, macromolecules and structures. Recently ROS have been recognized to regulate
many cellular responses to physical and chemical stimuli. Apoptosis is the ultimate cell
response to injury. When cell functions are fundamentally compromised, a cell can, on its
own initiative, or in response to cytokine messengers from neighboring cells, commit
Apoptosis is a gene directed process of cellular deletion that establishes
an equilibrium between cell birth and cell death.
This is an important
defense against many types of biological damage such as radiation, viral infections, drug
toxicity, and cancer. By this process, the cell can exert a direct control on its own
death, sacrificing itself to protect its host.
vary widely among different cell types and depend upon the nature of the apoptotic
stimulus, but some characteristics are common to all. An apoptotic cell shrinks, fragments
its DNA into small ladders, and activates specific endonucleases and proteases which form
membrane-bounded blebs that can be engulfed and digested by neighboring tissue cells or
macrophages without causing inflammation.
There is evidence of
a direct involvement of the cellular redox status in the activation and the functioning of
the apoptosis machinery.
Cell redox status
acts as the "consensus switch" for apoptosis execution. Bcl-2 as a gene product
is an important inhibitor of apoptosis. Bcl-2 acts in an antioxidant pathway, and its
function can be somehow substituted by other antioxidants. Antioxidants can act as
pro-apoptotic inducers in some cell types, such as smooth muscle cells, and as
anti-apoptotic agents in other models.
NF-kB transcription controls the expression of
different genes of fundamental importance in many pathophysiological conditions. NF-kB has also been demonstrated to play a key role in viral activation,
and different kinds of neoplasia.
Cytokine killer cell
activity against tumor cells is amplified by NF-kB inhibitors. The fact that some
antioxidants have already been demonstrated to be strong inhibitors of NF-kB activation
may be one of the pathways by which they protect against cancers naturally, and also opens
a promising avenue in the association between Tumor Necrosis Factor (TNF) and antioxidants
in cancer therapy.
NF-kB activity, and
therefore cell destiny, can be modulated by antioxidants, and this contributes to our
understanding of the biochemistry of disease and to the development of therapeutic