Purines and Cancer
I was recently in Greece for my son’s wedding. I was on faculty at their university while they were attending the school and had spoken to their frat. At the wedding, one of the frat brothers, having learned that I warned about the link between pork, shellfish, and cancer, made a dismissive comment about that as if there was nothing behind the idea.
At that time (2006), my 1987 assumption had some but little proof. We have learned a lot since then.
"Given the numerous connections between cancer and diet, I want to present a simple argument against consuming high-purine foods in relation to cancer. Some may have misunderstood my past comments and concluded that I advocate against eating meat. This is not the case—I believe that the American diet often lacks high-quality meat, which is one of the few foods, along with milk and eggs, that can sustain a person almost exclusively."
To further clarify, I mean animals that are primarily scavengers, so there is a combination of their diet and their high purine-producing metabolism. Both Jewish and Muslim traditions advocate for these diets, but few adhere to them.
There are a few exceptions. Anchovies, sardines, herring, and mackerel have sufficient fatty acids, especially omega-3 fatty acids, to more than offset any issues with purines. Organ meats have such high nutrient density that they qualify for exemption.
Before beginning, one final note: Highly processed meats, such as beef hot dogs or processed meat sticks, should be consumed sparingly, ideally a few times per year.
There are several key points about the relationship between purine signaling and cancer:
A. Purine metabolism and signaling play crucial roles in cancer development and progression. Purines are essential components for DNA/RNA synthesis and cell proliferation. Cancer cells often have enhanced purine biosynthesis to support rapid growth. Purines are also your basic energy molecules (ATP-ADP and GTP-GDP), and rapidly growing cells demand energy, and so the cells set up mechanisms for producing these.
Extracellular purines like ATP and GTP, adenosine, and guanine modulate immune responses and tumor-host interactions in the tumor microenvironment.
B. The tumor microenvironment has unusually high concentrations of ATP and adenosine. Adenosine is a major immunosuppressive factor in tumors. Without suppressing the immune system, cancer cells would suffer apoptosis. Immune suppression is generated by the sequential hydrolysis of extracellular ATP by CD39 and CD73 enzymes. Targeting these pathways (e.g., CD73) or adenosine receptors (e.g., A2A) can relieve immunosuppression and inhibit tumor growth in preclinical models.
Of great concern, but unstudied to my knowledge, is whether purine signaling switches neutrophil function from the destruction of a cancer cell to the constructive support of those cells.
C. Purinergic signaling affects multiple aspects of cancer biology. It modulates cell proliferation, migration, invasion, and metastasis in various cancer types. Purinergic receptors like P2X7 and P2Y2 are involved in promoting tumor growth and metastasis in many cancers.
Yes, the effects can vary. In some cases, purinergic signaling may also inhibit tumor growth. Remember, these are normal functions of cells, which, in cancer, have significant dysfunctions. Purine signaling in a known factor in genetic dysfunction.
D. Purine metabolism is distributed across different cell types in the tumor in a cancer-specific manner. There is intercellular crosstalk that shapes purine metabolism and signaling in the tumor ecosystem. Understanding this has therapeutic potential.
领英推荐
Inhibiting the P2X7 receptor on cancer and immune cells strongly inhibits experimental tumor growth. Adenosine pathway inhibitors are being explored clinically as cancer immunotherapies.
Purine metabolism and signaling are intricately involved in tumor biology through effects on cancer cells, immune cells, and the tumor microenvironment. This pathway presents opportunities for novel therapeutic approaches in cancer treatment.
(Ref.: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889871/ and https://www.cell.com/cell-reports/pdf/S2211-1247%2823%2901654-6.pdf )
Then, there is the relationship between Bradykinin and Purine Signaling.
There is a significant relationship between bradykinin and purine signaling, particularly in the context of cancer and neurological processes.
Interaction in signaling pathways was discovered. Bradykinin and ATP-mediated signaling may interact via multiple pathways. This interaction can influence various cellular processes, especially in glial cells and tumors. Glial blastoma killed my cousin and a friend who was a popular local newscaster.
Bradykinin has been shown to increase the resensitization of purinergic receptor signaling. In U87 astrocytoma cells, preincubation with bradykinin significantly increased the response to a second application of ATP. Both bradykinin and purinergic signaling play roles in inflammation and pain perception, which can be exaggerated in cancer (my father’s deadly squamous cell carcinoma was accompanied by extreme pain). Purinergic receptors are involved in pain transmission, and bradykinin released during tissue damage or inflammation could influence nociception by increasing resensitization of P2Y purinergic receptors.
Also, in metastasis of cancer cells themselves. Both kinin (bradykinin) and purine signaling contribute to neuroblastoma metastasis. Bradykinin has been found to induce P2X7B expression, promoting neuroblastoma metastasis in bone marrow by utilizing high extracellular ATP levels as a growth, seeding, and anti-apoptosis stimulus.
(Ref,: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889871/ and also https://ppm.wum.edu.pl/docstore/download/WUM92a272aafe644cbf9613dc76182321d2/0e698095-3eef-4922-a61e-768afcf56b48-wcag.pdf?entityType=article )
There are neurological implications between bradykinin and purinergic signaling that have implications for various neurological conditions. Both systems have been implicated in processes such as blood-brain barrier permeability, neuronal differentiation, and neurotransmitter release.
Physiological stress responses: Both systems are involved in stress responses. Bradykinin system genes have been associated with anxiety disorders in humans, while purinergic signaling is known to play a role in stress-related physiological responses.
The relationship between bradykinin and purine signaling is complex and multifaceted, involving interactions in cellular signaling pathways, cancer progression, pain perception, neurological processes, and stress responses. This interaction presents opportunities for further research and potential therapeutic interventions in various physiological and pathological conditions.
Be careful what you eat. Your life depends on good food.