EGCG is a substance extracted from green tea and represents up to 30% of its dry mass. The tea plant has been used in China for at least 6000 years and is one of Asia’s most important everyday drinks. In opposition to black tea, oxidation, i.e., the decomposition of the leaves by oxygen, is prevented during the drying process by roasting, steaming, or brief heating. Thus, almost all the ingredients 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 secondary plant substances that have health-promoting effects belong to polyphenols.
It has been known for decades that green tea and thus EGCG has an effect on cancer cells. How does this effect come about?
Let us first consider 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 being read. Switching genes on or off helps the cell to adapt flexibly to different environmental conditions. As a result, EGCG influences genes that have cancer-inhibiting and life-prolonging effects [1]. For example, various studies show that daily consumption of green tea or corresponding supplements can reduce the risk of developing or re-developing breast cancer[2].
Another effect is related to the Toll-like receptor 4. The scientist who discovered it and later won the Nobel Prize, Nüsslein-Vollhard, was so enthusiastic about the influence of the receptor in the fruit fly that she called it by the German word “toll.” Unfortunately, stimulation of this receptor in humans does little that is so great. In fact, more inflammatory messengers are released, and cancer cells are stimulated to grow. EGCG, along with other substances such as curcumin, 6-shogaol, and sulforaphane, now inhibits Toll-like receptor 4 and thus the growth of tumor cells.[3]
An important ability for tumors is to form blood vessels. Cancer cells achieve this by secreting the blood vessel-forming factor VEGF. This molecule or the associated receptor is an important target of modern oncological drugs. EGCG inhibits the release of VEGF, thereby reducing the blood vessel supply that is important for the tumor and, at the same time stimulating natural cell death (apoptosis). The VEGF receptor is one of the tyrosine kinase receptors responsible for cancer cells’ rapid and aggressive growth. EGCG also inhibits other such receptors.[4]
In laboratory trials, EGCG is shown to inhibit or activate a myriad of receptors and metabolic pathways, equaling the effect of curcumin. Thus, it decreases protein levels of Bcl-2, Bcl-xl, xIAP, cIAP, NFκΒ, Hsp70, and Hsp90. The latter are heat shock proteins and protect the cancer cell from the effects of heat, among others. This makes the combination of EGCG with hyperthermia conceivable as a synergism. Other proteins are, in turn, increased, such as Bad, Bax, Fas/CD95, cytochrome c, Apaf-1, AIF, GADD153, GRP78, and caspase-3, -7,-8, and -9. Caspases initiate natural cell death in tumor cells. Inhibition and stimulation of various proteins orchestrate between them, resulting in 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. It is interesting to note that cancer cells capable of metastasis form a specific receptor to which EGCG binds, a green tea receptor, so to say, and which, when blocked, limits or prevents the tumor cells’ ability to metastasize. Thus, besides the natural compound amygdalin, it is the only substance that can prevent tumor spread.[6]
So what makes cancer cells so difficult to attack? The slowly dividing tumor stem cells are resistant to chemotherapeutic agents because they can only attack dividing cells. Fortunately, there is an abundance among natural substances that can destroy stem cells. In addition to EGCG, these are curcumin, resveratrol, 6-shogaol, sulphoraphane, and indole-3-carbinols, both of which are found in broccoli, among others.[7]
As with other natural substances, there are concerns that EGCG may inhibit the function of chemotherapeutic agents. However, it can improve the effectiveness of many cytostatic drugs and thus represents a chemosensitizer, i.e., a substance that makes tumor cells resistant to chemotherapeutic agents.[8] Only the protease inhibitor bortezomib, used in so-called multiple myeloma, is limited in its effectiveness by green tea.[9] EGCG is also used in the treatment of cancer.
Due to its influence on numerous receptors and metabolic pathways in the tumor cell, EGCG is effective against various tumors, such as breast, colon, ovarian, pancreatic, and prostate cancer, at least in cell and animal studies. In benign tissue proliferations, such as endometriosis or fibroids, EGCG is also effective.[10] EGCG also appears to be effective against glioblastoma cells, cells of a malignant brain tumor for which conventional medicine has few effective methods. [11]
In addition to its multiple effects on cancer, EGCG also has positive effects on other ailments, such as neurodegenerative and cardiovascular diseases. It also appears to have a positive effect on diabetes. Among other things, blood glucose levels rise 50% less after a meal when green tea is enjoyed with it.[12]
In contrast to curcumin or 6-shogaol, for example, EGCG is a substance that is water-soluble and thus better absorbed. It can therefore also be well supplied orally. When preparing green tea, it should be noted that the water should not boil (about 80°C), and the tea should steep for about 5 minutes. It is useful to add some vitamin C powder to prevent premature oxidation. For a few years, EGCG is also available as an infusion. This, of course, allows higher activity levels and better effects than purely oral administration. Since liver values can rise in high dosages, which can never be achieved by drinking tea, blood monitoring is useful during infusion therapy.
In addition, it is also possible to evaluate the possible efficacy on the individual tumor cells of the patients.
Conclusion: EGCG from green tea is an effective enrichment for complementary and alternative cancer medicine and is also suitable for preventing various diseases.
Ressources
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[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.
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[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.
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[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.
