In a tumor, even without treatment, a substantial number of cancer cells spontaneously die each day. This is due to the high rate of cell proliferation and the unstable nature of cancer cells, which often have defects in their DNA repair mechanisms and can be more prone to apoptosis (programmed cell death) or necrosis (cell death due to injury or disease). Scientists discovered that when cancer cells die, either spontaneously or from treatment such as chemotherapy, cell-free chromatin particles are released into the tumor microenvironment, where they are readily internalized by surviving cancer cells and inflict DNA damage, inflammation, immune suppression, increased toxicity from chemotherapy, and ultimately, more cancer.
Our DNA is stored on our chromosomes as densely packed units called chromatin which contains DNA and proteins called histones. This configuration prevents the long strands of DNA from becoming tangled and plays an important role in stabilizing the DNA during cell division, preventing DNA damage, and maintaining normal gene expression. Cell-free chromatin particles are composed of tiny fragments of DNA and histones without other cellular components. These particles are released from cancer cells undergoing apoptosis—the mechanism a cell undertakes for self-destruction, activated when the cell senses significant self-damage.
Scientists also found that cell-free chromatin particles are released into the bloodstream from the billions of normal cells that die each day as we age. These particles readily enter healthy cells and integrate into their DNA. This leads to DNA damage, mitochondrial dysfunction, activation of apoptotic and inflammatory pathways, and impairment of mitochondrial function. This process triggers a vicious cycle and ongoing chain reaction that perpetuates the aging process and increases the risk of cancer.
Some scientists believe that the lifelong assault on healthy cells by internalized cell-free chromatin particles may not only be the chief underlying cause of the aging process and cancer but also may act as a global instigator of other age-associated disorders, including cardiovascular disease, diabetes, sepsis, and Alzheimer’s disease. Fortunately, scientists may have found a way to safely neutralize cell-free chromatin particles.
Scientists discovered that very minute and specific oral doses of resveratrol and copper (click here) generate oxygen radicals in the stomach. These radicals are readily absorbed into the circulation and permeate the extracellular spaces, and deactivate cell-free chromatin particles. In an animal model, this was found to downregulate several biological hallmarks of aging and neurodegeneration. In a human model using patients with advanced oral cancer, it was found that deactivating cell-free chromatin particles downregulated the hallmarks of cancer, as well as five immune checkpoint (suppressor) proteins. This data suggests that prolonged treatment with resveratrol and copper may have the potential to induce healing without having to directly kill cancer cells.
In conclusion, this exciting area of research offers potential strategies for combating cancer and perhaps even aging itself. As we deepen our understanding of the role of cell-free chromatin particles and explore ways to neutralize them, we may find ourselves on the brink of significant advancements in human health and longevity.
Comments: It is important to note that higher doses of resveratrol and copper were far less effective than lower doses. Also, the combination of resveratrol and copper was found to target 21 out of 23 biomarkers representing 10 hallmarks of cancer. The two exceptions were VEGFA (angiogenesis) and GLUT1 (cellular energetics). Apigenin has been found to inhibit VEGFA and GLUT1. Adding a bioavailable form of this compound might allow one to target all 23 biomarkers and improve treatment outcomes even further.
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