Friday Hope: Guarding the Guardian: Cruciferous Vegetables and their Compounds

Compounds that upregulate p53 expression may be of great therapeutic value in preventing/treating SARS-CoV-2/Spike Protein infection/exposure.

It has become well established that SARS-CoV-2 and its Spike Protein interact with/interfere with p53, the anti-cancer protein knows as the “Guardian of the Genome.” I believe that finding natural sources which upregulate p53 may not only ameliorate the severity of a SARS-CoV-2 infection or Spike Protein exposure but may also help prevent the inducement of cancer which downregulating p53 can cause. 

What is p53? 

The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. 

The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. 

Because p53 is essential for regulating DNA repair and cell division, it has been nicknamed the "guardian of the genome." 

TP53 gene 
https://medlineplus.gov/genetics/gene/tp53/ 

As you have read, p53 is a very important protein which is essential in protecting the genome and stopping cells with mutated or damaged DNA (ie cancer cells) from proliferating. As mentioned above, the Spike Protein of SARS-CoV-2 interacts with this essential protein. 

S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor Protein p53 and BRCA: an In Silico Study 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324311/ 

This may explain the recent rise in “turbocancers” and recurring cancers. It would therefore make sense to “guard” this “guardian.” Fortunately there are natural compounds which do precisely this – and they are readily available, although Papa Bush may not consume them as he was very outspoken in his dislike of broccoli. 

Cruciferous vegetables happen to contain compounds which directly and indirectly promote the expression of p53.  

In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the “guardian of the genome,” the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. 

Not only can cruciferous vegetables upregulate p53, they can help protect the genome itself. A double layer of protection, if you will. 

Some studies have reported the anticarcinogenic activity of several metabolites found in cruciferous vegetables. For example, glucosinolates, a secondary metabolite mainly found in cruciferous plants, display activity in preventing the development and progression of gastrointestinal cancers as well as in treating these cancers (11). To date, the existence of more than 130 glucosinolates has been reported which can be classified into three major structural groups i.e., aliphatic, indole, and aromatic glucosinolates (12). Biologically, the parent glucosinolate possesses negligible activity in preventing cancer progression. However, once it is converted into its derivatives, such as isothiocyanates, thiocyanates, nitriles, and indoles, the biological activity becomes potent. This conversion is mediated by the action of myrosinases during the mechanical digestion (e.g., chewing and cutting) of the vegetables (13). The anticancer activity of the cruciferous metabolites might be associated with several proposed mechanisms of action. It has been suggested that isothiocyanates and indoles play a pivotal role in regulating cell growth and cell cycle arrest which is essential in repairing the damaged DNA so that this prevents DNA alteration. The pro-apoptotic activity of these metabolites has also been reported. Other putative mechanisms include their activity in modulating oxidative stress and preventing the occurrence of angiogenesis (7). Anticancer activities of these metabolites are closely linked to their ability in upregulating p53 and its related target genes, e.g., p21 (14–16). 

If you wish to know the major compounds themselves, should you be looking for supplements, they are: 

Isothiocyanates, indole-3-carbinol, and phytoalexins. Note that sulforaphane is one of these. 

The conclusion of an article I am referencing sums everything up very nicely. 

A synopsis of the cancer-preventive potential of numerous Brassicaceae family members has been reported in this review. Even though there is a strong correlation between the prevention of carcinogenesis and consumption of cruciferous vegetables, it must be emphasized that many more studies are needed to fully understand the influence of these functional foods bioactive compounds on the human body. The upcoming experiments must specifically address the questions of bioavailability, stability, transport, and metabolism. These substances may have synergistic effects. It needs to be confirmed in further studies. In terms of the cancer-preventive characteristics of phytochemicals included in these veggies, the additional effects of typical food preparation techniques constitute another component that has yet to be fully investigated. Numerous studies aided in the acceptance of dietary agents as cancer treatment options. Due to their anti-tumorigenic and anti-proliferative competences, cruciferous vegetables are abundant with many functional bioactive compounds that have noteworthy inhibitory effects on different pathways of cancer cells. These veggies are advantageous because they are precursors to glucosinolates, which are precursors to isothiocyanates like sulforaphane and indoles like indole-3-carbinol. HDAC and DNMT overexpression, as well as miRNA misexpression, are common features of most malignancies. I3C, SFN, and I3C are regulators and inhibitors of these processes, and their usage causes malignant cell lines to seem more normal and healthier. With the inclusion of SFN and I3C, an increase in programmed cell death, as well as substantial reductions in uncontrolled cell proliferation, have been observed. Studies showed that functional bioactive compounds from cruciferous vegetables are potential candidates to fight cancer. Future research will likely focus on determining the epigenetic events influenced by the bioactive components of cruciferous vegetables and their importance in not just cancer prevention but also a variety of other biological systems. 

Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers 
https://www.frontiersin.org/articles/10.3389/fnut.2022.951935/full 

The above is a work of medical research and not medical advice. As with all medicines and supplements check with your Primary Care Provider before using any medicines or supplements. 

A joyous and blessed weekend to all!