Epigallocatechin gallate (egcg) in cancer

EGCG is a substance extracted from green tea and makes up 30% of its dry matter. Tea has been used in China for at least 6,000 years and is one of the most important everyday beverages in Asia. Unlike black tea, oxidation, i.e. decomposition of the leaves by oxygen, is prevented during drying by roasting, steaming or briefly heating. In this way, almost all components of the fresh plant are preserved.

From a chemical point of view, EGCG belongs to the catechins and these to the so-called polyphenols, which are characterized by aromatic ring structures. Many of the secondary plant substances that have a beneficial effect on health belong to polyphenols.

It has been known for decades that green tea and thus EGCG works against cancer cells. How does this effect occur?

First, let's look at the epigenetic effect. This means that although all the genetic information is in the DNA of the genes, only a fraction of it is actually read. Turning genes on or off helps the cell flexibly adapt to different environmental conditions. EGCG now affects genes that have anti-cancer and life-prolonging effects [1]. For example, various studies show that daily consumption of green tea or corresponding preparations can reduce the risk of developing breast cancer or its recurrence. [2]/sup>

Another effect affects Toll-like receptor 4. The discoverer and later winner of the Nobel Prize Nüsslein-Vollhard was so enthusiastic about the effect of the receptor in the fruit fly that she gave it the German word "toll". Unfortunately, stimulation of this receptor has little effect in humans. The messengers of inflammation are increasingly released and cancer cells are stimulated to grow. EGCG, together with other substances such as curcumin, 6-shogaol, sulforaphane, inhibits toll-like receptor 4 and thus the growth of tumor cells. [3]

One ability that is important for a tumor is the ability to form blood vessels. Cancer cells achieve this by releasing the factor VEGF, which forms blood vessels. This molecule and its associated receptor is an important target of modern oncology drugs. EGCG inhibits the release of VEGF, thereby reducing the blood vessel supply that is important to the tumor while stimulating natural cell death (apoptosis). The VEGF receptor belongs to the tyrosine kinase receptors responsible for the rapid and aggressive growth of cancer cells. Other of these receptors are also inhibited by EGCG. [4]

Laboratory tests have shown that EGCG inhibits or activates a number of receptors and metabolic pathways and is therefore equivalent to the effect of curcumin. It reduces the levels of Bcl-2, Bcl-xl, xIAP, cIAP, NFKΒ, Hsp70 and Hsp90 proteins. The latter are heat shock proteins and, among other things, protect the cancer cell from the effects of heat. This makes the combination of EGCG with hyperthermia conceivable as a synergism. On the other hand, other proteins such as Bad, Bax, Fas/CD95, Cytochrome c, Apaf-1, AIF, GADD153, GRP78 and caspase-3, -7, -8 and -9 are increased. Caspases initiate natural cell death in tumor cells. The coordination between inhibition and stimulation of various proteins leads to tumor growth inhibition or cancer cell death. [5]

What makes cancer so dangerous? It is primarily the ability to metastasize and invade and destroy vital organs. Interestingly, cancer cells that are able to metastasize create a specific receptor that EGCG binds to, the green tea receptor, so to speak, and which, when blocked, limits or prevents the ability of tumor cells to metastasize. Along with the natural substance, amygdalin is the only substance that can prevent the spread of the tumor. [6]

And what makes cancer cells so difficult to attack? They are slow-dividing tumor stem cells that are resistant to chemotherapy drugs because they can only attack dividing cells. Fortunately, there are many natural substances that can destroy stem cells. In addition to EGCG, it is curcumin, resveratrol, 6-shogaol, sulfuraphane and indole-3-carbinol, both of which are found in broccoli, among others. [7]

As with other natural substances, there are concerns with EGCG that it could inhibit the function of chemotherapy agents. In fact, however, it is able to improve the effect of a large number of cytostatics and is therefore a chemosensitizer, i.e. a substance that makes tumor cells resistant to chemotherapeutics. [8] Only the protease inhibitor bortezomib used in the so-called multiple myeloma is limited in effectiveness by green tea. [9]

By affecting many receptors and metabolic pathways in the tumor cell, EGCG is effective against a large number of tumors such as breast, colon, ovarian, pancreatic and prostate cancer, at least in cell and animal experiments. EGCG is also effective for benign tissue growths such as endometriosis or fibroids. [10] EGCG also appears to be effective against glioblastoma cells, malignant brain tumor cells that conventional medicine has almost no effective methods against. [11]

In addition to various effects on cancer, EGCG also has positive effects on other conditions, such as neurodegenerative and cardiovascular diseases. It also seems to have a positive effect on diabetes. Among other things, blood sugar levels rise 50% less after a meal if you enjoy green tea with it. [12]

Unlike, for example, curcumin or 6-shogaol, EGCG is a substance that is soluble in water and is therefore better absorbed. So it can also be taken orally. When preparing green tea, remember that the water should no longer boil (approx. 80°C) and the tea should steep for about 5 minutes. To prevent premature oxidation, it makes sense to add some vitamin C powder. EGCG has also been available as an infusion for several years. This of course means that higher active levels and better effects can be achieved than with purely oral administration. Since liver values can increase in high doses, which are never achieved by drinking tea, blood tests are useful in infusion therapy.

In addition, however, it is also possible to test possible effectiveness on the relevant tumor cells of the patient.

Conclusion: EGCG from green tea is an effective addition to complementary and alternative cancer medicine and is also suitable as a prevention of a wide range of diseases.

Resources

  • [1] Daniel M, Tollefsbol TO. Epigenetic linkage of aging, cancer and nutrition. J Exp Biol. 2015 Jan 1;218(Pt 1):59-70. doi: 10.1242/jeb.107110. PMID: 25568452; PMCID: PMC4286704.
  • [2] Gianfredi V, Nucci D, Abalsamo A, Acito M, Villarini M, Moretti M, Realdon S. Green Tea Consumption and Risk of Breast Cancer and Recurrence-A Systematic Review and Meta-Analysis of Observational Studies. Nutrients. 2018 Dec 3;10(12):1886. doi: 10.3390/nu10121886. PMID: 30513889; PMCID: PMC6316745.
  • [3] Chen CY, Kao CL, Liu CM. The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway. Int J Mol Sci. 2018 Sep 12;19(9):2729. doi: 10.3390/ijms19092729. PMID: 30213077; PMCID: PMC6164406.
  • [4] Shimizu M, Adachi S, Masuda M, Kozawa O, Moriwaki H. Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases. Mol Nutr Food Res. 2011 Jun;55(6):832-43. doi: 10.1002/mnfr.201000622. Epub 2011 May 2. PMID: 21538846.
  • [5] Wu PP, Kuo SC, Huang WW, Yang JS, Lai KC, Chen HJ, Lin KL, Chiu YJ, Huang LJ, Chung JG. (-)-Epigallocatechin gallate induced apoptosis in human adrenal cancer NCI-H295 cells through caspase-dependent and caspase-independent pathway. Anticancer Res. 2009 Apr;29(4):1435-42. PMID: 1941439
  • [6] Tachibana H, Koga K, Fujimura Y, Yamada K. A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol. 2004 Apr;11(4):380-1. doi: 10.1038/nsmb743. Epub 2004 Mar 14. PMID: 15024383.
  • [7] Dandawate PR, Subramaniam D, Jensen RA, Anant S. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy. Semin Cancer Biol. 2016 Oct;40-41:192-208. doi: 10.1016/j.semcancer.2016.09.001. Epub 2016 Sep 5. PMID: 27609747; PMCID: PMC5565737.
  • [8] Lecumberri E, Dupertuis YM, Miralbell R, Pichard C. Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin Nutr. 2013 Dec;32(6):894-903. doi: 10.1016/j.clnu.2013.03.008. Epub 2013 Mar 15. PMID: 23582951.
  • [9] Modernelli A, Naponelli V, Giovanna Troglio M, Bonacini M, Ramazzina I, Bettuzzi S, Rizzi F. EGCG antagonizes Bortezomib cytotoxicity in prostate cancer cells by an autophagic mechanism. Sci Rep. 2015 Oct 16;5:15270. doi: 10.1038/srep15270. PMID: 26471237; PMCID: PMC4607952.
  • [10] Laschke MW, Schwender C, Scheuer C, Vollmar B, Menger MD. Epigallocatechin-3-gallate inhibits estrogen-induced activation of endometrial cells in vitro and causes regression of endometriotic lesions in vivo. Hum Reprod. 2008 Oct;23(10):2308-18. doi: 10.1093/humrep/den245. Epub 2008 Jul 4. PMID: 18603648.
  • [11] Grube S, Ewald C, Kögler C, Lawson McLean A, Kalff R, Walter J. Achievable Central Nervous System Concentrations of the Green Tea Catechin EGCG Induce Stress in Glioblastoma Cells in Vitro. Nutr Cancer. 2018 Oct;70(7):1145-1158. doi: 10.1080/01635581.2018.1495239. Epub 2018 Sep 10. PMID: 30198785.
  • [12] Forester SC, Gu Y, Lambert JD. Inhibition of starch digestion by the green tea polyphenol, (-)-epigallocatechin-3-gallate. Mol Nutr Food Res. 2012 Nov;56(11):1647-54. doi: 10.1002/mnfr.201200206. Epub 2012 Oct 5. PMID: 23038646; PMCID: PMC3683549.

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