TP53, p53 and cancer

TP53, p53 and cancer

A deficiency in p53 seems to lie behind between at least half and probably most cancer tumours; here we review what p53 is and how you might restore its cancer-restricting actions.


Many ’experts’ miscategorise TP53, or p53.

Firstly, it refers to a protein - Tumour protein 53 (TP53), or tumour antigen p53.

In fact, more correctly, it is a group of proteins including p63 and p73. 

These proteins regulate cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled manner. The p53 protein keeps your cells dividing at a consistent, ‘healthy’ pace (1). 

A review by scientists at the NIH shows p53 has been found in the amniotic fluid in the womb, where it has a critical role in regulating the division of stem cells, in part converting them from rapidly dividing cells to a more normal pace, and helping them ‘differentiate’ into liver, kidney, ocular, lung cells etc. etc. Stem cells grow rapidly in the foetus for the first 50 days, then begin differentiating into your various body parts and settling down to divide at a calmer rate. Stem cells are also produced in your bone marrow for the rest of your life, and they are your repair ‘blanks’ that can convert into any cell you need (2). p53 has regulatory effects against cancer stem cells and suppresses them.

P53 activates genes. For example, accumulation of p53 in embryonic stem cells activates transcription of the target genes MDM2, p21, puma and noxa (3). In the research, p53 presence was at high levels in cells after radiation damage. 

Thus, p53 is involved in repair and ‘normal’ growth.

P53 and your power stations

Each of us has a small amount of DNA (about 37 genes) contained in the mitochondria. These genes are passed solely from the mother to the baby and largely control mitochondrial function. P53 controls mitochondrial function. It can alter the mitochondrial membrane’s permeability and it can regulate glucose metabolism in these power stations. Overall, it's actions are based inside the cell as a whole (in the cytoplasm). It has been called the Guardian of the mitochondrial genome.

It suppresses irregular energy production and thus cancer. It activates genes involved in apoptosis and cell cycle regulation triggering apoptosis, or ferroptosis, and inhibiting autophagy (4). 

P53 and cancer as a reversible metabolic disease

This is why many scientists now argue that cancer is a metabolic disease. Indeed, p53 has multiple and powerful functions in cell cycle arrest, senescence, cell death, repair of DNA damage, and mitophagy and one way it seems to operate tumour suppression is by adjusting the metabolism of iron, lipids, glutathione peroxidase 4, reactive oxygen species, and amino acids via a canonical pathway and sometimes this can give rise to a process of ferroptosis as the form of cancer cell death (5).

Because p53 proteins regulate cancer cells, it is often dubbed a Tumour Suppressor gene, and because of its many apparent roles, some of which are still not fully understood, it has also been called the Guardian of the Genome. But its primary actions seem to have more to do with the power stations or mitochondria.

Some research studies report that at least half of cancers are associated with p53 deficiency (6), while others imply almost all cancer tumours have p53 functional deficiency. Importantly, there's a growing concensus that, if you can regain at least partial p53 function, you can reverse the cancer process (7).

Was Gerson almost right?

Love him or hate him, Dr Max Gerson argued for much of this 80 years ago. His view of cancer, if I can put it simply, was that metabolic issues caused higher sodium levels in mitochondria at the expense of potassium, and that with every round of the Krebs cycle, sodium salts were produced rather than potassium salts, and these made the mitochondria slightly more acidic, and less effective. If you think of the power stations as little batteries, this acidity and efficiency loss caused them to power down. The p53 gene needs good energy levels, and without them it switches off - a deficiency, rather than a mutation (which would require a DNA sequence change). However, far less power was required by another gene, the ras gene, which makes cells divide rapidly and out of control.

The Gerson therapy has many similarities to the colourful Mediterranean Diet, but Gerson did not talk about the importance of magnesium as we do in this ideal diet. The Rainbow Diet is more than a diet - it is a lifestyle. Even sleep (melatonin) has been shown to help restore p53.

Certainly, the researchers from California showed that restoring the p53 gene, even in part, could correct or destroy the errant mitochondria of cancer cells (7).

What else might cause a deficiency in p53?

* CHEK2 and p53

CHEK2 is an inherited mutation; along with BRCA1, BRCA2 and PALB2. 7% of people have these inherited mutations. People with CHEK 2 are also shown to have p53 deficiency. This feature is more common in colorectal cancer (8). 

* MDM2 and p53

The MDM2 oncogene is a major negative regulator of p53 and inhibits the activity of p53 and reduces its protein stability. High MDM2, low p53. MDM2, p53, and the p53-MDM2 pathway represent well-documented targets for preventing and/or treating cancer. Many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability, increasing p53 levels and promoting anticancer activity in both p53-dependent and p53-independent manners (9).

Which Cancers are p53 deficient?

All. In Breast cancer at least 35% have been shown to exhibit p53 deficiency. In a meta-analysis (14), it states that the biggest issue seems to be detecting p53 deficiency (because it is not a genetic 'mutation). Levels could be far higher. Certainly, in Prostate cancer p53 deficiency was thought to only be present in advanced cases, but now it has been shown in early stage too 'at an unexpectedly high level' (15).

A review on colorectal cancer states that 43% of Colorectal cancer tumours, no longer have wild-type (normal) p53 (17); in lung cancer, a review by Stanford School of Medicine, talks of p53's role in preventing Lung cancer of being a player in normal, healthy lung tissue regeneration (18); and in Sarcoma, researchers identified nine sarcoma types, both bone (osteosarcoma) and soft-tissue sarcoma, which wild-type p53 plays a major role in preventing (16). The researchers talk of how modern techniques are showing significant p53 deficiencies as a major factor in sarcoma.

How does this translate into survival? In one study (19) on Oesophageal cancer, p53 deficiency was found in 59% of tumours. 80% of poorly differentiated tumours were p53 deficient, whereas in moderate/well differentiated tumours the figure was 56%. p53 deficiency increased significantly, the more hot drinks were consumed and this was associated with a lower survival rate. In a study (20) on follicular lymphoma, only 6% of cancers were p53 deficient, but this was linked to shorter. survival times. At the other extreme, 96% of ovarian cancers are p53 deficient (21).

How would you know if you are p53 deficient?

Interestingly, on the new Guardiant360 test that many people are now offered by the UK's NHS, p53 is not one of the 40 genes measured. But then, it is not a mutated (altered) gene. It is just turned off!

The DATAR test (from DATAR Cancer Genetics) does measure breast cancer, and recently prostate cancer, and has provided evidence that three of my breast cancer ladies (one Er+ve and two TNBC) are p53 deficient.

How might people with cancer reverse a p53 deficiency?

i) A diet high in minerals particularly iron, omega 3 fish oils, olive oil and olive leaf extract, amino acids, potassium and magnesium. We have research on each of these. For example, magnesium has been shown to encourage p53 cancer cell apoptosis (10).

ii) Niclosamide - this anthelmintic drug attacks and ‘uncouples’ cells that are p53 deficient with research showing it can reduce tumours by 50% if p53 deficient. It inhibits oxidative phosphorylation and stimulates adenosine triphosphatase activity in the mitochondria.

iii) IP-6 - research on breast cancer, colorectal cancer, prostate cancer and brain tumours has shown that this natural compound from bran can upregulate the p53 and p21 genes (11)

iv) Resveratrol, genistein, berberine and triptolide (from the Thunder God Vine) all have shown the ability to inhibit MDM2 and help to restore p53 (9). Turmeric has been shown to inhibit MDM2 and stabilise p53 in prostate cancer in vitro and in vivo by researchers at the University of Alabama (12).

We have more correctors of p53 in our Metabolic anti-cancer protocol.

Go to: A metabolic Protocol to correct p53 deficiency

The Bottom line on p53

There is absolutely no doubt that we still have more to learn about p53. The issue seems more one of deficiency than mutation; and a number of studies suggest it is possible to correct that deficiency. Since many of the natural compounds are in the Rainbow Diet, that would be a good place to start, as would looking into Niclosamide and IP-6. If you have cancer, why would you not at least try to restore your cellular power supplies and p53, the ‘Guardian of your mitochondrial genome’.

Go to: Cancer - why you’re not doomed




  1. The p53 family in differentiation and tumorigenesis; Thorston Stiewe; Nature Reviews Cancer volume 7, pages 165167 (2007)


  1. An Updated View of the Roles of p53 in Embryonic Stem Cells; Gamze Ayaz et al; Stem Cells. 2022 Oct 21;40(10):883-891


  1. Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage; Valeriva Solozobova et al; BMC Cell Biology volume 10, Article number: 46 (2009)


  1. Cytoplasmic functions of the tumour suppressor p53; Douglas R Green; Review Nature, 2009 Apr 30;458(7242):1127-30


  1. Ferroptosis and the bidirectional regulatory factor p53; Ren Xu et al; Cell Death Discovery volume 9, Article number: 197 (2023)


  1. Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis; Hudei Wei et al; Nature Communications volume 12, Article number: 2280 (2021)


  1. Partial p53 reactivation is sufficient to induce cancer regression; Boris Klimovich et al; Journal of Experimental & Clinical Cancer Research volume 41, Article number: 80 (2022)


  1. Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer; Julita Machlowska et al; Oncol Lett, 2021 May;21(5):348.


  1. Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine; Jiang-Jiang Qin et al; Genes Dis. 2018 Sep; 5(3): 204219.


  1. Controlled release of hydrogen by implantation of magnesium induces P53-mediated tumor cells apoptosis; Rui Zan et al; Bioactive Materials; Volume 9, March 2022, Pages 385-396


  1. Up-regulation of the tumor suppressor gene p53 and WAF1 gene expression by IP6 in HT-29 human colon carcinoma cell line - I T Saied Anticancer Res, 1998 May-Jun;18(3A):1479-84.


  1. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway; Mao Li,, Zhuo Zhang et al; Cancer Res;. 2007 Mar 1;67(5):1988-96


  1. p53 as guardian of the mitochondrial genome; Ji-Hoon Park et al; FEBS Lett; 2016 Apr;590(7):924-34.


  1. TP53 Mutations and Outcomes in Breast Cancer; A Shahbandi et al; Trends Cancer. 2020 Feb; 6(2): 98–110


  1. Revisiting the Role of p53 in Prostate Cancer; Miriam Teroerde et al; May 27, 2021, Exon pubs


  1. TP53 in bone and soft tissue sarcomas; Elizabeth Thoenen et al; Pharmacol Ther. 2019 Oct; 202: 149–164


  1. The Role of p53 Signaling in Colorectal Cancer; Magdelena Liebl et al; Cancers (Basel). 2021 May; 13(9)


  1. Tissue-regeneration program underlies lung-cancer suppression; Kaiser M. Nature

  2. p53 alterations in oesophageal cancer: AG Casson et al; Mol Pathol. 1998 Apr; 51(2): 71–79.

  3. P53 mutations in lymphomas: position matters; Arnold J. Levine,  Evan Vosburgh; Blood (2008) 112 (8): 2997–2998.

  4. The Challenges and Prospects of p53-Based Therapies in Ovarian Cancer; Bryce Wallis et al; Biomolecules. 2023



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