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The P53 tumor suppressor gene: understanding P53-based anticancer therapies utilizing dietary agents.


The P53 tumor suppressor gene, which has been dubbed both the "Guardian of the Genome" (Lane 1992) and Science "Molecule of the Year," is directly involved in the initiation of apoptosis and programmed cell death, to prevent an accumulation of abnormal cells. However, apoptosis evasion is a characteristic feature of human cancers that promote tumor formation and progression. (1) Presently, P53 is known to play a key role in practically all types of human cancers, and the mutation or loss of P53 gene function can be identified in more than 50% of all human cancer cases worldwide. (2)

Frequency of P53 Mutations

70% in lung cancer

60% in cancers of colon, head, neck, ovary, bladder

45% in stomach cancer

35%-40% in breast cancer

Recent data have shown that, in addition to losing transcriptional function, mutant P53 gains oncogenic functions termed GOF (gain of function) that drive cell migration, invasion, and metastases. (3,4) The notion for mutant P53 GOF theory is supported by recent studies using mutated P53-blocked mice which display a broader tumor spectrum, increased aggressiveness and metastatic potential as compared with their P53-null counterparts. (5,6) Similarly, in human cancers mutant P53 expression has been linked with a poor prognosis. (7) Therefore, mutant P53 function raises the possibility that the mutant protein may be a good target for designing novel therapies.

The P53 pathway seems to play a critical role in therapeutic response both as a diagnostic and marker in the prognosis of therapeutic treatment effects.

The inability of most cancers to undergo apoptosis in response to appropriate stimuli is a key cause of treatment failure, presenting one of the major yet unsolved problems in oncology. (8)


Programmed cell death, called apoptosis, is a fundamentally important process that prevents an accumulation of genetically abnormal cells. Apoptosis induction often appears to be related to the production process of P53 protein. This follows the activation of the tumor suppressor gene as a stress response to any DNA damage within a cell nucleus. (9) In normal, unstressed cells, P53 is expressed at a very low level; the half-life of the protein does not exceed 20 minutes.

Active P53 binds to target DNA and determines the choice between triggering cell cycle arrests at a checkpoint to allow DNA repair or activating a special molecular pathway leading to the self-destruction of a cell through apoptosis. Both alternatives provide any organism with genetic stability.

The critical role of P53 is made evident by the fact that it is mutated in approximately 50% to 70% of all human cancers. In fact, P53 is the most commonly mutated gene in human cancer.

In human malignancies, very often there are mutations or a loss of alleles in the gene located on the chromosome 17P. More than 500 mutations in the P53 gene have been discovered, although they are not equal in terms of biological activity.

The mutated gene in transformed cells leads to protein confirmation changes and the accumulation of very stable mutant forms of P53 in the nucleus. All types of mutated P53 are likely to be ineffective in maintaining a nontumorigenic cellular phenotype when compared with a wild-type P53.

Wild-type P53, a nuclear phosphoprotein, has been shown to be a sequence specific transcription factor which induces the expression of P21, WAF1/C1 P1/Sdi-1, leading to a G1 arrest checkpoint to step up repair before DNA replication and contributes to normal cell proliferation; unless DNA replication is successful, the cells will be induced to undergo apoptosis. (10)

However, during a stress response from its P53 gene to any damage, recent findings suggest that P53 induces apoptosis by transactivating expression of the BAX gene mRNA to increase BAX protein and simultaneously inhibit the function of Bcl-2.n RNA proteins are homologs, though BAX acts as an accelerator of apoptosis while Bcl-2 serves to prolong survival. (12)

This suggests that P53 mutation not only serves to inactivate the proapoptotic P53 pathway but may also play an additional role in tumor progression. Mutant P53 itself provides a selective advantage to tumor cells and promotes tumor growth. Recent data suggest that expression of mutant P53 is not the equivalent of P53 loss, wherein mutant P53 can acquire new functions.

Bcl-2 activity upregulates in many types of cancer and correlates with cancer cell resistance to a wide spectrum of chemotherapy agents.'3 Overexpression of the antiapoptotic Bcl-2 proteins blocks cytochrome C release in mitochondria in response to a variety of stimuli, whereas the proapoptotic BAX protein releases cytochrome C that in turn activates an apoptotic cascade, while the loss of BAX is associated with tumor progression and shorter survival in metastatic breast cancer. (14)

BAX was the first identified P53-regulated, proapoptotic Bcl-2 family member. P53-responsive elements have been unequivocally identified in the BAX gene. (15) BAX is specifically required for PUMA (p53-upregulated modulator of apoptosis)-mediated apoptosis, and it also participates in the death response as an indirect target of P53 through PUMA and Noxa, both implicated in P53-dependent apoptosis. (16)

Some studies show that the loss of BAX is responsible for nearly half of the accelerated tumor growth in brain tumors that are related to loss of P53 function. (17) BAX is inactive in approximately one-third of invasive breast cancers; in a study of 119 women with metastatic breast cancer, it was found that patients whose tumors had lost BAX activity had poor responses to combination chemotherapy, faster time to tumor progression, and shorter overall survival. (18)

This may suggest that turning on this proapoptotic gene may be important for chemotherapy response, wherein one of the factors that can regulate BAX gene activity is the P53 tumor suppressor gene, which also simultaneously inhibits Bcl-2 during the process of apoptosis. Nevertheless because BAX proteins antagonize Bcl-2 antiapoptotic function, it is likely that the Bcl-2/BAX balance ratio determines both the susceptibility of a cell to apoptosis and therapeutic response to apoptosis stimuli. (19)

If apoptosis signaling is not initiated by nuclear P53 and/or the presence of a mutated P53 gene, loss of BAX, and overexpressed Bcl-2, this allows some cancer cells to divide unchecked after radiation or chemotherapy treatment, associated with cancer cell resistance, increased rate of tumor recurrence, and shorter patient survival. (20)

Another profound feature of malignant cells is their ability to induce angiogenesis necessary for tumor growth. Again, there is a clear correlation between mutant P53 GOF that facilitates angiogenesis by increasing the expression of VEGF, via interaction with E2F1 that induces the expression of ID4, which in turn promotes the expression of proangiogenic factors such as IL and GROa, thus eventually leading to increasing angiogenesis in cancerous tissues. (21,22) Other novel functions of mutant P53 GOF are shown through the activation of specific target genes EGFR/1, RAS, Myc, and interference with the TGFB growth arrest control pathway, downregulation of the E-cadherin cell-cell adhesion molecules to enhance motility, and tumor cell migration and invasion. (23)

We have new clues and important conceptualizations which indicate that tumors cannot be viewed simply as an uncontrolled proliferative mass, but rather as a cellular community, interacting with a microenvironment. (24,25) This is why targeting mutant P53 remains an urgent need to improve cancer treatment by increasing a cancer cell's sensitivity to apoptosis.

Therapeutic Strategy

Targeting mutant P53 and restoring the wild-type function of P53 tumor suppressor gene in tumor cells would be of potential therapeutic benefit and an attractive strategy for anticancer treatments. (26-27) Upon restoration of P53 transcriptional activity, the apoptosis pathway would predominate.

Many cancer cells escape apoptosis and become resistant to chemotherapy radiation or from destruction by the immune cells by endogenous cytotoxic T-cells and natural killer (NK) cells. If the oncogene Bcl-2 is highly expressed it confers greater resistance to cancer cells from attacking immune cells, increasing the urgent need for effective cancer therapies.

Furthermore, some of the P53 apoptosis targets such as BAX, PUMA, Noxa, and P21 could potentially be used as targets for gene therapy to increase the effectiveness of chemotherapy.

Dietary Agents that Induce Apoptosis with Chemo Preventive Effects

A large number of dietary agents can exert effects on the human genome either directly or indirectly to modulate gene expression. Extensive research during the last half-century demonstrated that numerous agents identified from fruits and vegetables can interfere with several signaling pathways and were validated as apoptosis inducers in research experiments.

These dietary agents include well-known, well-documented substances recommended for cancer prevention and therapy, such as curcumin (turmeric), resveratrol (grapes), genistein (soybean), capsaicin (red chili), ellagic acid (pomegranate), caffeic acid and phenyl ester (propolis), polyphenols (green tea), catechin (green tea), and indole-3-carbinol (cruciferous vegetables). (28-35)

They have all clearly accumulated evidence demonstrating their efficacy to induce apoptosis by modulation of the P53 independent pathway, BAX, BAK, targeting the antiapoptotic proteins, Bcl-2, and survivin gene so as to potentialize a chemotherapy/radiation regimen. Curcumin, for instance, has been found to inhibit the activity of NF-kB and Bcl-2, and increase P53 activity as well as sensitize cancer cells to cisplatin- and Taxol-induced apoptosis. (37) The combination of 5-Fu and genistein enhances therapeutic effects in colon cancer through the COX-2 pathway. (38) Genistein combined with docetaxel or gemcitabine significantly inhibited Bcl-2/ Bcl-xL, survivin, and induced P21 WAF1, suggesting that combination treatment regulates the important molecules in the apoptotic pathway. (39,40) Green tea and black tea cause induction of apoptosis accompanied with upregulation in BAX and a decrease in Bcl-2 proteins in prostate cancer cells. (41) Capsaicin-caused apoptosis in prostate cancer cells shows an increase of P53, P21, and BAX. (42) Curcumin downregulates the apoptosis suppressor proteins Bcl-2 and Bcl-xL in several cancer cell lines, thus increasing apoptosis overall. (43)

In human breast cancer cells, curcumin induces apoptosis through P53-dependent BAX induction; curcumin, resveratrol, and green tea polyphenols are also known to downregulate the expression of apoptosis suppressor proteins such as Bcl-2 and Bcl-X in several cancer cell lines. (44)

In human prostate carcinoma LNCaP cells, treatment with EGCG-induced apoptosis was associated with stabilization of P53, with an accompanying downregulation of NF-kB activity resulting in a decreased expression of the antiapoptotic Bcl-2. Overall dietary agents synergize with chemotherapeutic drugs, thereby reducing the toxicity of chemotherapeutic agents. (45)

Numerous studies continue to report that resveratrol exerts its anticancer effects by causing cell cycle arrest and inducing apoptosis in many different cancers. (46) These include colon adenocarcinoma cells (Caco-2), esophageal carcinoma cells, medulloblastoma cells, the highly invasive and metastatic breast cancer cell line MDA-MB-231, melanoma cells, pancreatic carcinoma cells, esophageal squamous carcinoma cells, and lung cancer cells.

A complete document concerning the modulation of apoptosis by active compounds for cancer therapy and their synergy with chemotherapeutic agent is available at


Deregulation of P53 has enormous influence on carcinogenesis as mutant P53, which can induce an increased epigenetic instability of tumor cells, facilitating and accelerating tumor evolution.

An increasing body of investigation has shown that inhibitor of apoptosis protein (lAPs) as Bcl-2, survivin, and so on, is now seen as diagnostic markers for early-stage malignancy and novel prognostic markers. (47) In addition these molecules have been validated as therapeutic targets. Accumulated evidence clearly indicates that dietary agents may play a critical role by targeting P53 and IAPs and improve chemotherapy regimen. Despite significant advances in cancer diagnosis and therapy, there is still little progress in the treatment of advanced disease.

Most modern medicines currently available for treating cancer are very expensive, toxic, and less effective in treating the disease. Therefore new effective ways to treat cancer have become a priority. Thus, one must investigate further in detail, dietary agents derived from natural sources without toxicity. Hopefully, they will find a place in the clinical management of patients with malignancy.

Case Reports

We have been measuring the activity of P53 pathway, BAX, Bcl-2, survivin, and P21 gene expression with a large number, variety, and grades of cancer patients, developing a targeting therapy that could restore mutant P53 to a normal wild-type function as a first step after gaining results to modulate BAX, inhibit the Bcl-2 and survivin antiapoptotic proteins. The targeting therapy includes dietary agents such as curcumin and other compounds empirically experimented upon by the author. It includes an extract of fish oils rich in oligopeptide, that contain short-chain amino acids shown to have efficiency to target mutant P53, fermented chlorella in tablets rich in vitamins, minerals, and nucleic acids. (48) The fermenting process increases the level of nutrients and absorptive power. Finally, an antioxidant compound was derived from modified vegetables and seeds, with low molecular weight having SOD-like activity. (49)

This targeting therapy, known as PSJ-53 therapy, had been first utilized in experiments to restore mutant P53 and proved by P53 gene expression and P53 protein testing. Later experiments in modulating BAX gene expression and targeting Bcl-2 and survivin antiapoptotic proteins were shown to potential ize the efficiency of chemotherapy and radiation. (50) Survivin, a unique member of the IAPs, inhibits caspase-7 and -9 and promotes both cell proliferation and angiogenesis. (51) Measuring and targeting survivin remains a major goal in response to antineoplastic agents. (52)

We present three cancer cases with blood analysis reports of P53 gene expression and mutated protein levels before and after the treatment, along with two cases with complete figures of the proapoptotic and antiapoptotic genes before and after treatment.

1. a case of multicancer recurrence.

2. remission of breast cancer

3. pancreatic cancer

4. recurrence of colon cancer

5. lung cancer

6. glioma


P53 pathway activity and other proapoptotic and antiapoptotic genes were evaluated by measuring protein concentration and the level of P53 gene expression, Bcl2, BAX, survivin, and P21 in the same peripheral venous blood obtained from patients in the clinic.

The enzyme-link immunosorbent assay (ELISA) was used together with the polymer chain reaction (PCR) to evaluate P53, BAX, survivin, and P21 gene expression levels and for the qualitative detection of P53 protein. Blood samples were collected in sterile tubes and sent to a laboratory specializing in molecular marker tests, which offers complete reports and discussion about each test. Survivin/P21: 0.53

We have clearly demonstrated that mutant P53 can be targeted together with other proapoptotic and antiapoptotic genes using dietary compounds, which for many patients has been proved with many scientific examples. This is only one example and not the publication of cancer cases followed over a 1- or 2-year period as we have done with many patients. This child has now been treated for over 2 years with excellent results, and has taken 5 blood analyses, which each time indicated what treatment should be done. However, my last article in the Townsend Letter 2014 showed complete cases relative to breast cancer with molecular marker testing done over a 1-year period and more. Step by step it showed improvement and the normal balance between the proapoptotic and antiapoptotic genes. (50)

New avenues are now focusing on targeting apoptosis in cancer, which include oncogenes, Bcl-2, and survivin that increases cancer cell resistance to chemotherapy/ radiation regimen, while scientific literature today has already accumulated thousands of articles on laboratory reports, theories, and studies.

We urgently need to put into clinical practice what we have discovered and learned. Targeting P53 and other genes remain one of the greatest challenges in the treatment of cancer. We have been working now for over 8 years with molecular markers as a diagnostic, prognosis, and follow up to treatment, selected the appropriate bioactive dietary compounds or anticancer agents, exceeding 1000 cases, blood tests, and successes. This may be an incentive for more doctors to venture into this new direction in order to achieve more beneficial results with patient treatment, especially in cases where we can verify the ones who would be refractory to chemotherapy and have a poor response. It is always best to first check through patient testing, to determine whether or not chemotherapy would be beneficial.


(1.) Hollsteen M, Sidrausky D, Volgestein B, Harris CC. P53 mutations in human cancers Science. July 5, 1991;253(5015)49-53.

(2.) Fulda S. Tumor resistance to apoptosis. Int J Cancer. 2009; 124:511-515.

(3.) Oren M, Rather V. Mutant P53 gain of function in cancer. Cold Spring Harb Perspect Biol. 2010. February:2(2).

(4.) Van Oijen MGCT, Slootweg PJ. Gain of function mutations in the tumor suppressor gene P53. Clin Cancer Res. June 2006:21-38.

(5.) Muller PAJ, Vousden KH, Norman JC. P53 and its mutants in tumor cell migration and invasion. J Cell Biol. January 2011;192(2)209-218.

(6.) Walerych D, Napoli M, Collavin L, Del Sal G. The rebel angel: mutant P53 as the driving oncogene in breast cancer. Carcinogenesis. 2012 Nov;33(11)2007-2017.

(7.) Baker L et al. P53 mutation, deprivation and poor prognosis in primary breast cancer. Br J Cancer. 2010;102:719-726.

(8.) Reeds JC. BCL-2 and the regulation of programmed cell death.) Cell Biol. 1994;124:1-6.

(9.) Lakin ND. Jackson SP. Regulation of P53 in response to DNA damage. Oncogene. 13 December 1999;18(53):7644-7655.

(10.) Macleod KF, Sherry N, Hannon G, et al. P53-dependent and independent expression of P21 during cell growth, differentiation and DNA damage. Genes Dev. August 25, 2014.

(11.) Miyashita T, Red JC. Tumor suppressor P53 is a direct transcriptional activator of the human BAX gene. Cell. 1995;80:293-299.

(12.) Ibid.

(13.) Del Bufalo D, Biraccio A, Leonetti C, Zupi G. BCL-2 overexpression enhances the metastatic potential of a human breast cancer line. FASEB I. Oct. 1997;950(11):947-952.

(14.) Krajewski C, Blomquist K, Franssila M, et al. Reduced expression of proapoptotic Bax is associated with poor response rate to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res. 1995;55:4471-4478.

(15.) Miyashita T, Krajewski S, Krajewska M, et al. Tumor suppressor or P53 is a regulator of BCL-2 and BAX gene expression in vitro and in vivo. Oncogene. 1994 June 9;6:1799-1805.

(16.) Yu J, Zhang L. No Puma no death: implications for P53-dependent apoptosis. Cancer Cell. October 2003;4(4):248-249.

(17.) Fueyo J, Gomez-Manzano C, McDonnell TJ. Regulation of cell cycle and apoptosis in Human brain tumors. In: Ali-Osman F, ed. Contemporary Cancer Research: Brain Tumors. Totowa, N): Humana Press Inc.; 2002:249-264.

(18.) Krajewski C, Blonquist K, Franssila M, et al. Reduced expression of pro-apoptotic gene BAX is associate with poor response rate to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res. 1995;55:4471-4478.

(19.) Scopa CD, Vagianos C, Kardamakis D, Kourelis TG, Kalofonos HP, Tsamandas AC. BCL-2/BAX ratio as a predictive marker for therapeutic response to radiotherapy in patient with colorectal cancer. Appl Immunohistochem Mol Morphol. 2001 Dec;9(4):329-334. December 2001;9(4):329-334.

(20.) Harina Y, Harina K, Shikata N, Oka A, Ohnishi T, Tanaka Y. Bax and BCL-2 expression predict response to radiotherapy in human cervical cancer. J Cancer Res Clin Oncol. 1998;124:503-510.

(21.) Farthang Ghabreman M, Goossens S, et al. P53 promotes VEGF expression and angiogenesis in the absence of an intact P21-Rb pathway. Cell Death Differ. 2013 Jul;20(7):888-897.

(22.) Fontemaggi G, Dell Orsos Triscinoglo D, et al. The execution of the transcriptional axis mutant P53, E2F1 and LD4 promotes tumor angiogenesis. Nature Struct Mol Biol. 2009;16:1086-1093.

(23.) Muller PAJ, Vousden KH, Norman JC. P53 and its mutants in tumor cell migration and invasion. J Cell Biol. January 2011;192(2)209-218.

(24.) Allinen M, Berouklim R, Car L, et al. Molecular characterization of the microenvironment in breast cancer cell. 2004;6:17-32.

(25.) Howlett AR, Bissell MJ. The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium Epithelium Cell Biol. 1993;2:79-89.

(26.) Bal L, Zhu W-G. P53 structure, functions and therapeutic applications. Cancer Mol. 2006;2(4): 141-153.

(27.) Schimmer AD. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. October 15, 2004;64:7183-7190.

(28.) Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23:363-398.

(29.) Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis and inhibits angiogenesis of LNCAP prostate cancer cells in vivo. Prostate. 2001;47:293-303.

(30.) Aggarvwal BB, Bhardway A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004;24(5A):2783-2840.

(31.) Li M, Zhang Z, Hill DL, Chen X, Wang H, Zhang R. Genistein a dietary isoflavone down-regulates the MDM2 oncogene at both transcriptional and posttranslational levels. Cancer Res. 2005;65(18):8200-8208.

(32.) Oyagbemi AA, Saba AB, Azeez Ol. Capsaicin: a novel chemopreventive molecule and its underlying molecular mechanism of action. Ind / Cancer. Jan/March 2010:47(1)53-58.

(33.) Narayanan BA, Geoffray O, Willingham MC, Re GG, Nixon DW. P53/P2 (WAF1/ C1P1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett. March 1999; 136(2):215-221.

(34.) Natarajan K, Singh S, Burke TR Jr, Grimberger D, Aggarwal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF.KB. Proc Nat Acad Sci USA. August 1996;93:9090-9095.

(35.) Baliga M, Meleth S, Katiyar S. Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma AT1 cells in vitro and in vivo systems. Clin Cancer Res. March 1, 2005;11(5)1918-1927.

(36.) Choi H-S, Cho M-C, Lee HG, Yoan D-Y. lndole-3-carbinol induces apoptosis through P53 activation of caspases-8 pathway in lung cancer A549 cells. Food Chem Toxicol. March 2010;48(88):883-890.

(37.) Han SS, Chung ST, Robertson DA, Ranjan D, Bondada S. Curcumin causes the growth arrest and apoptosis of B-cell lymphoma by down regulation of egr-1, C-myc, bcl-xl, NF kappa B, and P53. Clin Immunol. 1999;93(2):152-161.

(38.) Li Y, Bhuiyan M, Sarkar F. Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein. Oncogene. 1999;18:3166-3172.

(39.) Davis JN, Singh B, Bhuiyan M, Sarkar FH. Genistein-induced upregulation of P21/ WAF1, downregulation of cyclin B and induction of apoptosis in prostate cancer cells. Nutr Cancer. 1998;32:123-131.

(40.) Philip PA, Abbruzzere J, Sarkar FH. Molecular evidence for increased antitumor activity of gemicitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res. 2005;65:9064-9072.

(41.) Nakazato T, Ito K, Ikedo Y, Kizahi M. Green tea component, catechin, induce apoptosis of human malignant B cells via production of reactive oxygen species. Clin Cancer Res. 2005;11 (16):6040-6049.

(42.) Lin C-H, Lu W-C, Wang C-W, Chan Y-C, Chen M-K. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Ahem Med. 2013;13:46. doi: 10-1186/1472-6882-13-46.

(43.) Lu Z-D, Liu X-P, Zhao WJ, et al. Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro in vivo. Int J Clin Exp Pathol. 2014;7(6): 2818-2824.

(44.) Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induce apoptosis in human breast cancer cells through P53-dependent Bax induction. FEBS Lett. Feb. 13, 2002;512(1 -3):334-340.

(45.) Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 2006;71(2006):1397-1421.

(46.) Ahmand N, Adhami VM, Afaq F, Feyes DK, Mukhtar H. Resveratrol causes WAF-1/ P21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin Cancer Res. 2001 ;7(5):1466-1473.

(47.) Xiaoynan C, Longhang C, Jinghua W, et al. Survivin: a potential prognostic marker and chemoradiotherapeutic target for colorectal cancer. Ir J Med Sci. 2010; 179:327-335.

(48.) Jurasunas S, Taylor OG. How to target mutant P53 in a case of multiple cancer recurrence. Townsend Lett. August/Sept 2010;325/326:68-71.

(49.) Jurasunas S. Therapeutic application of a new low molecular antioxidant compound. Presented at: International Symposium on ROS and Nitrogen Species: Diagnostic, Preventive and Therapeutic value. July 8-12, 2002; St. Petersburg, Russia.

(50.) Jurasunas S. A complementary approach to breast cancer: a case with multiple liver metastases is free from disease. Townsend Lett. August/Sept 2014;68-72.

(51.) Shin S, Sung BJ, Cho YS, et al. Anti-apoptotic protein human survivin is a direct inhibitor ofcaspase-3 and -7. Biochemistry. 2001;40:1117-1123.

(52.) Mita AC, Mita MM, Nawrocki ST, Giles FJ. Survivin: Key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res. 2008;14:5000-5005.

Professor Serge Jurasunas, a frequent Townsend Letter contributor, will be the featured speaker at the Physician's Round Table Conference to be held in Tampa, Florida, January 29-31, 2016, together with other well-known integrative cancer doctors. He will present two lectures: "Health and Disease Begin in the Colon, As Seen through Iridology" (he will be signing his new expanded book on the subject), and "How to Understand Cancer from a Molecular Basis." He will show how cancer can be diagnosed earlier on and then treated with dietary agents.

For additional information, contact

Serge Jurasunas is an internationally well-known doctor of naturopathy and alternative medicine with over 40 years of experience in the treatment of cancer. He is developing innovative therapies in cancer treatment and is a pioneer in live blood analysis, dried blood oxidative stress, and iridology.

Dr. Jurasunas is busy working with P53 tumor suppressor gene and other molecular markers testing related to cancer patients and patients with high risk of cancer.

For more information and to learn about cancer treatment, molecular markers, and clinical cases at Holiterapias Clinic, please visit; e-mail: info@; phone: +351 213471117.

Table 1: Effects of PSJ-53 Therapy on the Tumor Suppressor P53 Pathway
M: Case of Multiple Cancer Recurrence

                    P53 protein level units/ml of plasma

No     Date of         Wild P53 Ref.       Mutated P53
     blood sample   range * <0.33 units/   Ref. range
      collection        ml of plasma          ND **

1     2 Feb 2009           ND **              26.1

2    18 May 2009            16.8              ND **

3    21 Sep 2009           156.0              ND **

No      P53 gene (wild
     expression level Ref.
     range * < [10.sup.6]
         copies/ml of

1      2.7 x [10.sup.5]

2      8.9 x [10.sup.11]

3      1.5 x [10.sup.13]

No   Comments

1    The blood sample was collected prior to
     PSJ-53 therapy

2    The blood sample was collected after a 3
     month course of PSJ-53 therapy

3    The blood sample was collected 4 months
     after completion of the PSJ-53 therapy
     during which time no further treatment was

Table 2: F: 48 Years Old: Breast Cancer--Breast
Cancer in Remission 2009

                    P53 protein level units/ml of plasma

No     Date of      Wild P53 Ref. range    Mutated P53
     blood sample   * < 0.33 units/ml of   Ref. range
      collection           plasma             ND **

1     2 Feb 2010           ND **              52.5

2    19 Apr 2010           10.99              ND **

No     P53 gene (wild     Comments
      expression level
       Ref. range * <
     [10.sub.6] copies/
        ml of plasma

1          52.245         The blood sample was
                          collected prior to
                          PSJ-53 therapy

2         170.000         The blood sample was
                          collected after a 2
                          month after
                          completion of the

The results clearly show the presence of mutated P53 prior
to PSJ-53 therapy. However, after 2 months of the treatment,
we reversed the mutant P53 to a normal wild-type function,
associated with an increase of the P53 therapy gene
expression and protein level during this period of time.

Table 3: F: 56 Years Old--Pancreatic Cancer--5
Years of Remission

                          P53 protein level
                          units/ml of plasma

No      Date of      Wild P53 Ref.   Mutated P53     P53 gene (wild
      blood sample   range * <0.33   Ref. range     expression level
       collection     units/ml of       ND **        Ref. range * <
                        plasma                     [10.sup.6] copies/
                                                      ml of plasma

1      4 May 2009        ND **          52.5             52.245

2     4 July 2009        10.99          ND **           170.000

3     17 Nov 2009        67.4           ND **       1.2 x [10.sup.6]

No    Comment

1     The blood sample was collected prior to
      PSJ-53 therapy

2     The blood sample was collected after a 2
      month after completion of the PSJ-53

3     The blood sample was collected after a 4
      month after completion of the PSJ-53

The results clearly show the presence of mutated P53 prior
to the PSJ-53 therapy. However, after 2 months of therapy
followed by 4 months of treatment, we reversed the mutant
P53 to a normal wild-type function, and gradually the P53
wild protein production rose to a high level, leading to
increased self-destruction of cancer cells.

Table 4: M: 81 Years Old: Recurrence of Colon Cancer--Liver

The patient refused chemotherapy but agreed to take some
radiation therapy. He was sent by his medical doctor to take
molecular markers testing to first check whether
radiotherapy would be efficient. P53, BAX, or P21 should be
active and sensitive to radiation, and increase selfdestruction
of cancer cells.

New Reference range: P53 protein level wild//0.10//1.00
units/ml of plasma

P53 gene expression:                  10-50 units/ml of plasma

Bcl-2 gene expression:                10 units

BAX gene expression:                  10-100 units

Survivin gene expression:             10 units

P21 gene expression:                  10-50 units

                      P53 protein level units/ml
                      of plasma

No    Date of blood   Wild P53 Ref.   Mutated P53   P53 gene (wild
         sample       range * <0.33   Ref. range      expression
       collection      units/ml of       ND **        level Ref.
                         plasma                       range * <
                                                     copies/ml of

1      1 Mar 2011         ND **          10.88          ND **
2      11 Jul 2011        ND **          ND **          1.180

No    Bcl-2    BAX    Survivin    P21

1      390    ND **     129      ND **
2     ND **    409     ND **     ND **

The results clearly show after 4 months of treatment a
significant improvement and reversal of the mutant P/53
tumor suppressor gene. However, the P53 gene didn't induce
the level of normal protein (often because of a blockage of
PUMA). BAX gene expression is now active as a pathway to
destroy cancer cells and the oncogene Bcl/2 and survivin are
not active due to the applied treatment. Therefore the new
pattern showed that cancer cells were destroyed and that
radiotherapy would be efficient, increasing the destruction
of cancer cells. The first report showed Bcl/2 and survivin
were slightly active (at risk) but after the treatment were
totally inhibited, which contributed to increase the
efficiency of chemotherapy/radiation regimen. After
radiation therapy and further treatment with natural
compounds, the patient was free from liver metastases.

Table 5: M: 50 Years Old--Lung Cancer

                     P53 protein level units/ml of plasma

     Date of blood   Wild P53 Ref.   Mutated P53   P53 gene (wild
No      sample       range * <0.33   Ref. range      expression
      collection      units/ml of       ND **        level Ref.
                        plasma                       range * <
                                                    copies/ml of

1     7 Jan 2013         ND **          16.26          ND **
2     11 Mar 2013         0.1           ND **            3

     P53 protein level units/ml of plasma

     Bcl-2   BAX   Survivin    P21

1     340    330    1.028      552
2      2      5       5       4.527

Ratio of the 1st Analysis
Bcl/BAX: 0.89
Ratio of the 2nd Analysis
Bcl/BAX: 2.5

Survivin/P21: 905.4--too high to make a ratio

The results clearly show after 2 months with PSJ-53 therapy
that we reversed mutant P53 to a wild type function, but P53
protein was produced only to a certain extent. However, we
have targeted Bcl-2 and especially the high expression of
survivin to a normal range and eliminated resistance in some
population of cancer cells and increased the selfdestruction
of cancer cells through chemotherapy-radiation
with a resultant decrease in lung nodule size. P21 gene
expression is very highly active (4.527) and promotes the
self-destruction of cancer cells. P21 is a P53-independent
channel to apoptosis and can be independent of P53 activated
by another channel such as the TGF-B. P21 is very sensitive
to radiation in destroying cancer cells.

Table 6: F: 8 Years Old--Glioma
Postponed chemotherapy after three
surgeries and poor results.

                      P53 protein level
                      units/ml of plasma

No      Date of       Wild P53 Ref.   Mutated P53   P53 gene (wild
      blood sample    range * <0.33   Ref. range      expression
       collection      units/ml of       ND **        level Ref.
                         plasma                       range * <
                                                     copies/ml of

1      6 Jan 2013          0.2           ND **          1.344
2      11 Mar 2013        16.4           ND **           820

No    Bcl-2    BAX    Survivin    P21

1     2.066   1.714    1.734     2.192
2      131    ND **    ND **      229
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Author:Jurasunas, Serge
Publication:Townsend Letter
Article Type:Report
Date:Aug 1, 2015
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