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Apoptosis, Antioxidants and NF-kB Activation

Reactive 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 suicide.

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.

Apoptosis features 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 strategies.

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Apoptosis of cancer cells induced naturally or by chemotherapy can be blocked by NF-kB proteins.Antioxidants inhibit NF-kB, helping to fight cancers.

Information and statements regarding dietary supplements herein has not been evaluated by the Food and Drug Administration and is not intended to diagnose, treat, cure, or prevent any disease. Nor is it meant to substitute for the advice provided by your health care provider. The efficacy of antioxidant supplementation for children and during pregnancy is not established . If you have or suspect that you have a medical problem, please contact your physician.

Network AntioxidantsTM and The First Defense Against AgingTM are trademarks of Cyberpac, Inc. Lester Packer, 1999. All Rights Reserved.

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