As a target for the selective killing of cancer cells was published in the US Library of Medicine in 2001 by the Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. Now almost 12 years later the Superoxide Dismutase - SOD is one of the technologies in the invention of the CC Formula as described in several areas of the patent filings
The principle of the SOD is to dismutate the superoxide anion into molecular oxygen and H2O2. This reaction is catalyzed by the SOD enzymes, which are ubiquitous in biological systems. The vast majority of these enzymes contain metal ions, usually Cu, Zn, or Mn, as cofactors. In addition to their important role in the metabolism of oxygen, SOD enzymes play a crucial role in the control of reactive oxygen species (ROS) and oxidative stress.
The first thing that is needed to understand the importance of the SOD is some basic information about ROS. Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can damage cells, proteins, and DNA. ROS are produced naturally as a by-product of normal cellular metabolism, but their levels can increase during times of stress, such as when the body is fighting an infection.
Excessive ROS can cause oxidative stress, which has been linked to a number of chronic diseases, including cancer. However, the body has several mechanisms for dealing with ROS, including the production of antioxidant enzymes like SOD.
This new application filing is a continuation-ín-part of U.S. application number 11/932,260 (filed October 31, 2007) which is a continuation-in-part of U.S. application number 11/616,317 (filed on December 27, 2006, now abandoned) Which is divisional of U.S. application number 10/027,692 (filed on December 20, 2001, now patent number 7,163,709).
Described in the patent, is the invention of an “artificial” SOD that can be easily applied and used for treating the over-production of superoxide. The disclosed subject is related to chemical composition and method of use for the treatment of ALS patients. A Cu/Zn superoxide dismutase (SOD) is disclosed that neutralizes the debilitating effects suffered by individuals that are producing excessive superoxide, causing the symptoms of ALS.
The overexpression of the cells toward the manufacture of superoxide has been linked to other neural disorders (eg. Down syndrome) and the use of the disclosed composition to treat other superoxide-related diseases is also contemplated.
The invention utilizes a new technology directed at a manufacturing process and efficient application of Cu/Zn SOD based on a ligand system. The composition counteracts the effects of the overproduction of superoxide by utilizing a ligand system that has the capability of permeating into the affected tissues and countering the overproduction of superoxide.
Superoxide dismutases (SOD) are essential enzymes that eliminate superoxide radicals (O2-) and thus protect cells from damage induced by free radicals. The active O2- production and low SOD activity in cancer cells may render the malignant cells highly dependent on SOD for survival and sensitive to inhibition of SOD. Here we report that certain estrogen derivatives selectively kill human leukemia cells but not normal lymphocytes.
Using complementary DNA microarray and biochemical approaches, we identify SOD as a target of this drug action and show that chemical modifications at the 2-carbon (2-OH, 2-OCH3) of the derivatives are essential for SOD inhibition and for apoptosis induction. Inhibition of SOD causes accumulation of cellular O2- and leads to free-radical-mediated damage to mitochondrial membranes, the release of cytochrome c from mitochondria, and apoptosis of the cancer cells.
Our results indicate that targeting that enzyme may be a promising approach to the selective killing of cancer cells and that mechanism-based combinations of SOD inhibitors with free-radical-producing agents may have clinical applications.
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.