Friday Hope: Vitamin D, p53 and the Spike Protein

Vitamin D may ameliorate the downregulation of tumor suppressor p53 induced by the Spike Protein.

Vitamin D3 inhibited the proliferation of MCF-7 (A) and MDA-MB-231 (B) cells through the upregulation of p53 and (B) the downregulation of Bcl2. In order to determine the molecular mechanisms responsible for vitamin D3-induced cell growth inhibition, MCF-7 cells were treated with increasing concentrations of vitamin D3, and protein lysates were collected. Western blotting analysis showed a visible increase in p53 expression (an indicator of apoptosis) and a decrease in Bcl2 (an indicator of cell survival) upon the treatment of cells with vitamin D3. Alpha-enolase was used as a control for protein loading. Cisplatin (Cis-200) was used as positive control. 

Once again, we gain further understanding as to why Vitamin D is so critical in the battle against the Spike Protein. As Millennials would say: Vitamin D FTW! 

One of the current great concerns of the world health community is the sudden rise in what has been termed “turbocancers.” Many have offered explanations ranging from energy drinks to red meat. (...) However, as readers of this Substack know, a likely candidate is the presence of the Spike Protein from SARS-CoV-2 and its suppression of a protein called p53.  

For those who are not certain of the mechanism, please allow me to explain. As mentioned, there is a protein in our cells called p53. This is known as a tumor suppressor.  

The p53 gene like the Rb gene, is a tumor suppressor gene, i.e., its activity stops the formation of tumors. If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood. This condition is rare, and is known as Li-Fraumeni syndrome. However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation. 

The p53 gene has been mapped to chromosome 17. In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the 'stop signal' for cell division. Thus cells divide uncontrollably, and form tumors. 

The p53 tumor suppressor protein 
https://www.ncbi.nlm.nih.gov/books/NBK22268/ 

The Spike Protein inhibits the expression of this protein, with potentially devastating effect. Please note that there was very well-known paper which called this out – and it was retracted. (...) Of course, I found the science sound and would never have retracted it. To avoid the consternation of some, should I quote that paper, another group of researchers have fortunately made the same finding, albeit in cancer cells. They should look further. 

We further observed that SARS-CoV-2 spike suppresses p53 transcriptional activity in cancer cells including after nutlin exposure of wild-type p53-, spike S2-expressing tumor cells and inhibits chemotherapy-induced p53 gene activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2. The suppressive effect of SARS-CoV-2 spike on p53-dependent gene activation provides a potential molecular mechanism by which SARS-CoV-2 infection may impact tumorigenesis, tumor progression and chemotherapy sensitivity. In fact, cisplatin-treated tumor cells expressing spike S2 were found to have increased cell viability as compared to control cells. 

SARS-CoV-2 spike S2 subunit inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells 
https://www.biorxiv.org/content/10.1101/2024.04.12.589252v1 

This is where Vitamin D enters the picture. Not only does Vitamin D have all the previously discussed benefits in combating SARS-CoV-2 and its Spike Protein (please search Vitamin D in this Substack’s archive), it also presents us with a new one: maintaining adequate Vitamin D levels may prevent the Spike Protein from inhibiting the expression of p53 as Vitamin D enhances the expression of this very same protein. 

In our study, the treatment of BC (Breast Cancer) cells with vit-D3 induced the expression of pro-apoptotic proteins p53 and Bax, G2/M cell growth arrest, reduced cell migration, and increased apoptosis (as demonstrated by elevated caspase-3/7 activity) in vitro. However, we have not tested the BC xenografts in mice, which may be considered a limitation of our study. Instead, EAC (Ehrlich Ascites Carcinoma) cells were used in our in vivo models. EAC cells represent mammary tumors and are widely used in cancer research [52]. Vit-D3 also retarded tumor growth in vivo via the inhibition of cell proliferation and the induction of EAC cell apoptosis. In the solid tumor model, vit-D3 reduced tumor size and tumor weight via the activation of necrotic cell death and the upregulation of caspase-3/7 and p53 expression. Supporting our findings, previous investigations demonstrated that vit-D3 treatment inhibited cancer growth via the elevated expression of cell cycle arrest proteins (p21 and p27) and increased activators and mediators of apoptosis, including caspase-3/7, p53, and Bax [53]. 

Vitamin D3 Inhibits the Viability of Breast Cancer Cells In Vitro and Ehrlich Ascites Carcinomas in Mice by Promoting Apoptosis and Cell Cycle Arrest and by Impeding Tumor Angiogenesis 
https://www.mdpi.com/2072-6694/15/19/4833 

I have always had a massive appreciation for Vitamin D. Indeed, it is one of the supplements I have taken regularly throughout my life. I did this even though, when in high school, my doctor told me “You don’t need vitamins, just eat healthy foods.” Needless to say, I have no regrets. 

Please remember that the above is a work of medical research and not medical advice. Please consult your Primary Care Provider before using any medication of supplement. 

The sun is finally out here in Northern Vermont after almost a week of cold and rain. Enjoying the late summer sun is something I am looking forward to. After all, it’s free Vitamin D. 

Thank you, as always, for your support, dialogue and readership. I am extremely grateful that more readers have become paid subscribers. As I have mentioned before, you are the wind beneath my wings. To that end, I will continue to take flight and discover.