Ivermectin and p53 expression
A potentially potent anti-tumor and anti-viral combination?
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SYNOPSIS
In Men In Black’s continuing saga of discovery related to Zinc deficiency and early treatment for the mitigation of RNA viruses, as well as cancer, we have found ourselves traveling down a multitude of “rabbit holes.” But none has been as fascinating and critically important as the link between the TP53/p53 gene/protein and Zinc deficiency, as well as the role that a modified version of the Zelenko Protocol can play in resolving this deficiency and enhancing p53 function.
p53, as a master regulatory gene, manages both our body’s interferon signaling and pathogenic “smoke detector” pathways, as well as binding to damaged DNA to prevent its unfettered division (cancer). Interferon is what triggers a “hey, we’ve been invaded by pathogens” response, signaling the immune system to take action. The same occurs with cells that possess damaged DNA. p53 binds to that damaged DNA, like genetic “handcuffs,” preventing the DNA strand from dividing until it is repaired or, failing that, targeting the errant cell for destruction, a process called apoptosis.
Thus, the more p53 expression that occurs in the face of a viral or tumor scenario, the greater our body’s ability to muster the requisite immunological defenses against them.
All of these revelations are the result of 4 1/2 years of research and analysis related to the Zelenko Protocol and the role of Zinc deficiency in our lives.
In concert with the Zinc-based Zelenko Protocol, we have also encountered various claims about Ivermectin and its antiviral activities. Now, we are increasingly hearing about its potential anti-cancer capabilities. But the one question that has evaded me is the exact potential mechanism of action in this regard. I believe I have just stumbled upon something significant, and it relates, of course, to p53, the Guardian of the Genome.
TREATMENT
Ivermectin is an award winning antiparasitic drug, derived from a fermentation by-product of Streptomyces avermitilis bacteria, discovered, in all places, a soil sample from a golf course in in Japan. It has proven to be a Broad Spectrum antiparasitic, primarily used to treat River Blindness (Onchocerciasis) caused by Filarial worms. However, it appears to also be effective against other pathogens can cause Malaria and Elephantiasis and other parasites. For those readers not versed in the history of Ivermectin’s use, this is good historical review written by its discoverer, Satoshi Omura, who was co-awarded the 2015 Nobel prize in Physiology for his feat.
There are many resources available discussing Ivermectin’s anti-viral qualities available via a web search, but what I wanted to focus on is the growing belief that Ivermectin also displays potent anti-cancer qualities which have remained a bit unclear and uncertain.
Recently, actually this morning to be exact, I decided to conduct a “fishing expedition”, as I often do to reveal “rabbit holes” and queried Ivermectin against p53.
The result was this article in Frontiers in Pharmacology from 2021. Though, admittedly, I haven’t yet tore through the entire article, this one paragraph caught my attention regarding how Ivermectin upregulates the expression of the p53 protein, with the obvious anti-tumor ramifications:
Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth
Song et al. (2019) revealed that ivermectin induced glioma cells apoptosis by upregulating the expressions of p53 and Bax, downregulating Bcl-2, activating cleaved caspase-3, and cleaved caspase-9. Zhang et al. (2019) observed that the ratio of Bax/Bcl-2 in the cytoplasm increased in ivermectin-induced apoptosis of Hela cells.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.717529/full
And then that link led to Song’s paper from 2018, discussing Ivermectin and Gliomas (Brain tumors). Sadly, it lurks behind a paywall, as can often be the case on research of any significance. It’s only for the “professional” researchers.
Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo
What we hope the reader can derive from this is that anything that promotes the synthesis of p53 appears to be a positive benefit for both antiviral and anti-tumor defenses. To date, after months of digging, I have yet to find any form of cancer that is resistant to the DNA-binding function of p53 when it is functioning properly. Thus, if Ivermectin can promote increased expression of p53, and, in the presence of sufficient free intracellular zinc to permit it to properly fold and function, we may have revealed an additional mechanism of action with implications for both cancer treatment and defense against all forms of pathogenic viruses.
Overexpression of p53 and Zinc deficiency
However, that increased expression has a caveat. IF p53 is over expressed in the absence of sufficient Zinc, it would, logically speaking, result in greater mutant p53 formation due to misfolding of the p53 protein. Thus, with any anticancer, or even antiviral protocol that incorporates Ivermectin, it should include supplemental Zinc and the requisite Zinc Ionophore/Metallochaperone. I would suggest EGCG. Given its apparent associated with p53, it would be the Zinc Ionophore of choice for me. However, I remain open to additional suggestions.
Epigallocatechin gallate (EGCG), which is derived from green tea, is well known for its chemopreventive activity. Several studies have shown that p53 plays an important role in the activity of EGCG; however, the mechanism by which EGCG regulates p53 requires further investigation. In the present study, we showed that EGCG inhibits anchorage-independent growth of human lung cancer cells by upregulating p53 expression. EGCG treatment can substantially increase p53 stability, promote nuclear localization of p53 and decrease nuclear accumulation of MDM2.
Curcumin
Curcumin is also reported to play a role in the stability of p53 and increasing its expression. I’m also adding it to my list of Zinc Ionophores, though I remain uncertain of its potency versus EGCG and Quercetin. But there’s certainly little downside to its use, I would opine.
Natural food sources that can assist in the expression of p53
Recall that p53 is the protein coded for by the TP53 gene at position 17 on our DNA. It’s part of our genetic code. It’s the body’s natural means of mitigating oxidative stress induced DNA damage incurred by a variety of environmental factors. It is critical to the proper function of our entire immune system response against pathogens, and tumors. It regulates that interferon “smoke detector” that triggers our immune response. If it’s not functioning properly, everything downstream of it’s control will also be impaired. So it makes sense to investigate dietary sources that promote it’s activity. This link, discussing the benefits of Cruciferous vegetables is far too extensive to cover fully in the remainder of this article, but is well worth clicking on and reviewing. Though, in these current days of mass agriculture, it is more expensive to rely up quality organic, it may be well worth the financial sacrifice in endeavouring to do so.
Summation
Ivermectin appears to have an additional benefit in promoting p53 expression. However, as we’ve already experienced, it has been demonized and heavily restricted in its availability to the general public. While I appreciate discovering a new mechanism for its anti-cancer properties, I remain mindful that it is not a natural food source, but rather a fermentation derived from a microbial source. The strategy of PROTOCOL-Z is to identify naturally occurring ingredients available to all of us without prescription (or proscription by those with a medical profit motive).
p53 is ubiquitous in every cell of our body, including stem cells. Its role in binding damaged DNA is also ubiquitous and pertinent to every form of cancer. That is why it is called the Guardian of the Genome. No matter the cause of DNA damage, p53’s role is to halt its division into an errant, unfettered cancerous tumor. p53 is the body’s form of genetic “chemotherapy,” and its proper function should be enhanced by all means.
To make p53 fold and function properly, Zinc is required. Zinc deficiency, in the presence of drugs like Ivermectin to boost p53 expression, may be counterproductive if that p53 misfolds into its pathogenic, contagious mutant form. Therefore, a daily focus on elemental Zinc intake, in combination with a natural Zinc ionophore/metallochaperone and Ivermectin, should be strongly considered.
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