Green tea extract EGCG an effective chemopreventive polyphenol

"We were in Japan once where they had 30 kinds of green tea. I thought there was one." Billy Corgan

EGCG, also known as epigallocatechin-3-gallate, is the main polyphenol in green tea (Camellia sinensis). In particular, it is found in high concentration in the dried leaves of green tea (7380 mg per 100 g), white tea (4245 mg per 100 g), and in smaller quantities in black tea (936 mg per 100 g). Trace amounts are found in apple skin, plums, onions, hazelnuts, pecans and carob powder (at 109 mg per 100 g).

So far, different epidemiological studies (Source Review 2019: "Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine") have indicated that consumption of green tea has the potential of reducing the risk of many chronic diseases, such as cardiovascular diseases and cancer.

In particular, EGCG possesses various biological effects including

• anti-obesity,
• anti-hyperuricemia,
• anti-oxidative,
• anti-viral,
• anti-bacterial,
• anti-infective,
• anti-angiogenic,
• anti-inflammatory and
• anti-cancer.

Regarding its anti-cancer activities, EGCG has anti-cancer effects in a variety of cancer cells including lung, colorectal, prostate, stomach, liver, cervical, breast (Source: "Fighting breast cancer with natural compounds backed by science" Via Vocal), leukemia, renal (Source: "Fighting renal cell carcinoma with natural compounds backed by science" Via Vocal), gastric and bladder cancers.

Among its anti-cancer activities, EGCG exhibits multiple pharmacological actions, including

• the suppression of cell growth, proliferation and metastasis,
• the suppression of angiogenesis (Source: "Fighting angiogenesis with natural compounds backed by science" Via Vocal),
• induction of apoptosis, and
• enhancement of anti-cancer immunity.

For example, EGCG can inhibit cell proliferation through multiple ways in human bladder cancer, breast cancer and non-small cell lung cancer cell lines, and can inhibit tumour growth in gastric cancer xenograft mice. It also induces apoptosis in human oral cancer, head and neck cancer, non-small cell lung cancer and breast cancer cell lines.

Moreover, EGCG can induce autophagy (Source: "Artemisinin a class of remarkable drugs" Via Vocal). By inducing autophagy (via reactive oxygen species induction) can enhance EGCG-induced cell death in human mesothelioma (a type of cancer that develops from the thin layer of tissue that covers many of the internal organs) and primary effusion lymphoma (a distinct B-cell non-Hodgkin lymphoma caused by human herpesvirus type 8, also referred to as Kaposi sarcoma-associated herpesvirus) cell lines.

EGCG also suppresses metastasis in human melanoma cell lines and lung metastasis in mice. In addition, EGCG suppresses tumour angiogenesis in human non-small-cell lung carcinoma cell lines and non-small-cell lung carcinoma xenograft mice.

ER stress also plays an important role in EGCG-induced cell death.

ER is the endoplasmic reticulum, in essence, the transportation system of the eukaryotic cell. Is a large, dynamic, netlike labyrinth of branching tubules and flattened sacs extending throughout the cytosol that serves many roles in the cell including protein synthesis for the rest of the cell to function, calcium storage and lipid metabolism.

The ER is equipped with transmembrane receptors that can detect the onset of ER stress, and accordingly initiate the "unfolded protein response" to restore the normal function of ER. If a particular stress is prolonged, or the adaptive response fails, apoptotic cell death emerge.

We know for example, that EGCG can mediate apoptosis through ER stress in hepatocellular carcinoma cell lines. Similarly, EGCG causes 78-kDa glucose-regulated protein (that facilitates folding and assembly of nascent polypeptides and prevents their misfolding and aggregation) accumulation in the ER, which eventually up-regulates ER stress markers, and shifts cells into pro-apoptotic ER stress status.

Anti-tumour immunotherapy

Interferon γ, a cytokine that is critical for the innate and adaptive immunity, is a strong inducer of indoleamine 2,3-dioxygenase, which is an enzyme involved in the induction of tumour-immune-tolerance, that is a phenomenon that occurs when a tumour develops mechanisms to evade effective immunosurveillance.

Hopefully, EGCG has a significant inhibitory effect on interferon-γ-induced indoleamine 2,3-dioxygenase enzyme expression in human colorectal cancer cell lines, indicating that EGCG might be useful for chemoprevention in colorectal cancer treatment and for anti-tumour immunotherapy.

Although, EGCG has numerous biological activities, it has low oil solubility, metabolic instability and poor bioavailability.

Therefore, EGCG analogs and EGCG-loaded nanoparticles (EGCG-SLN, DT-EGCG-nanoethosomes, FCS-EGCG-NPs, EGCG-dispersed selenium nanoparticles, EGCG-loaded microspheres and many more) have been developed in the last decade, and they all have been reported to enhance EGCG's anti-cancer effects.

For example, peracetate-protected (−)-EGCG is a prodrug of EGCG obtained by modifying EGCG, and it was demonstrated to increase the bioavailability of EGCG and to inhibit angiogenesis in endometrial cancer xenograft mice. Moreover, EGCG-DHA (docosahexaenoic) ester, a lipophilic derivative of EGCG, showed improved anti-oxidative effects compared to EGCG, and suppressed colon carcinogenesis in mice.

Overall, all the EGCG analogs tested so far can improve the targeting ability and efficacy of EGCG, which greatly promote the clinical application and development of EGCG analogs.

EGCG also exerts synergistic effects with anti-cancer agents in various cancer cells, such as cisplatin, oxaliplatin, temozolomide, resveratrol, doxorubicin, vardena l, curcumin, erlotinib.

For instance, EGCG can enhance the sensitivity of cisplatin (a chemotherapy medication used to treat a number of cancers), which results in the accumulation of cellular cisplatin and cisplatin–DNA adducts in human ovarian cancer cells, and additionally the combination of EGCG and cisplatin suppresses the tumour growth in human ovarian cancer cell xenograft mice.

Moreover, the combined treatment of low concentration of EGCG and curcumin remarkably inhibited cell and tumour growth in human non-small-cell lung carcinoma cells, and non-small-cell lung carcinoma xenograft mice through cell cycle arrest.

To evaluate the tolerance, safety, pharmacokinetics and efficacy of EGCG in humans, clinical trials have been or are currently being conducted for cancer treatment.

During a phase I clinical trial, patients with breast cancer received adjuvant radiotherapy and a EGCG solution for the treatment of dermatitis and it was found that the maximum dose (660 μM) of EGCG was well tolerated. The conclusion was that EGCG was effective for treating radiation induced-dermatitis.

Moreover, a phase II clinical trial was conducted to investigate the benefits of EGCG as a treatment for acute radiation-induced esophagitis for patients with stage III lung cancer, and the oral administration of EGCG was shown to be effective.

How much green tea or powdered extract of green tea should you consume per day?

EGCG may be administered as a powdered extract of green tea (each gram of this extract provides 400–500 mg of EGCG), and an appropriate dose has been extrapolated from anti-angiogenic activity in rodent experiments as well as from a phase I study in humans. In practice, lower total daily doses of 2–4 g standardised green tea extract (95% polyphenols and 60% catechins) are usually prescribed, and 250 ml of brewed green tea typically contains about 50–100 mg of EGCG (Source).

However, daily intakes equal to or above 800 mg of EGCG per day can increase the blood levels of transaminases, an indicator of liver damage, so a safe intake level of 338 mg of EGCG per day has been recommended. In general, you should be very cautious if you’re considering taking this supplement.

In fact, in 2018 the European Food Safety Authority stated that daily intake of 800 mg EGCG or more could increase risk of liver damage. The degree of toxicity varies by person, suggesting that it is potentiated by genetic predisposition and the diet eaten during the period of ingestion, or other factors.

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PS:

Place the water in a tea kettle and heat until it almost boils. Then add 1 teaspoon of gunpowder green tea (a form of tea in which each leaf has been rolled into a small round pellet) to your cup and pour the hot water over your tea.

Infuse your tea for at least one minute. The longer you infuse, the stronger your tea it becomes. But, after three minutes of infusion a bitter flavour might result. Finally, add some honey and mint leaves and enjoy.

“Teatime is a chance to slow down, pull back and appreciate our surroundings.” - Letitia Baldrige

Letitia Baldrige was an American etiquette expert, public relations executive and author who was most famous for serving as Jacqueline Kennedy's Social Secretary.