Cancer Treatment: Pro-oxidant cocktail (Resveratrol + Copper) deactivates cell-free chromatin particles (cfChPs)

Billions of cells die in the body every day, and cell-free chromatin particles (cfChPs) which are released from them enter into the extracellular compartments of the body, including into the circulation.

cfChPs are known to readily enter into healthy cells to damage their DNA and activate apoptotic and inflammatory pathways.

Hypothesis: Lifelong assault on healthy cells by cfChPs is the underlying cause of ageing, and that ageing could be retarded by deactivating extra-cellular cfChPs. The extra-cellular cfChPs can be effected by oxygen radicals that are generated upon admixing the nutraceuticals resveratrol and copper (R–Cu).

Prolonged administration of R–Cu would retard biological hallmarks of ageing?

#Prooxidant (#resveratrol (R) + #copper ) #downregulates multiple #biological hallmarks of #ageing & #neurodegeneration in mice. R is a well-known #antioxidant but acts as #prooxidant in presence of Cu.

R–Cu treatment led to reduction of several biological hallmarks of ageing in brain cells which included

1. Telomere attrition
2. Amyloid deposition
3. DNA damage
4. Apoptosis
5. Inflammation
6. Senescence
7. Aneuploidy
8. Mitochondrial dysfunction.

R–Cu treatment also led to significant reduction in blood levels of glucose, cholesterol and C-reactive protein.

These findings suggest that cfChPs may act as global instigators of ageing and neurodegeneration, and that therapeutic use of R–Cu may help to make healthy ageing an attainable goal.

Reversal of telomere shortening by R–Cu may suggest that telomere shortening could be a consequence of DNA damage inflicted by cfChPs which shear off telomere ends causing them to shorten.

Sources:

• Pal, K., Raghuram, G.V., Dsouza, J. et al. A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration in mice. Sci Rep 12, 17209 (2022). https://doi.org/10.1038/s41598-022-21388-w
• Mittra, I. et al. Cell-free chromatin from dying #cancer cells integrate into genomes of bystander healthy cells to induce DNA damage and inflammation. Cell Death Discov. 3, 1–14 (2017).
• Mittra, I. et al. Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin. Ann. Oncol. 28, 2119–2127 (2017).
• Kirolikar, S. et al. Prevention of radiation-induced bystander effects by agents that inactivate cell-free chromatin released from irradiated dying cells. Cell Death Dis. 9, 1–16 (2018).
• Mittra, I. et al. Cell-free chromatin particles released from dying host cells are global instigators of endotoxin sepsis in mice. PLoS ONE 15, 1–22 (2020).
• Narita, M. Cellular senescence and chromatin organisation. Br. J. Cancer 96, 686–691 (2007).
• Tripathy, B. K. et al. Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells. bioRxiv https://doi.org/10.1101/2021.12.30.474529 (2021).