p53 interacts directly with anti-apoptotic proteins such as Bax and Bcl2 to induce apoptosis 21, 22 and is also involved in the anti‑senescent effect of EGCG 23, 24.įull length p53 is composed of an N-terminal domain (NTD), a DNA-binding domain (DBD), a tetramerization domain (TET), and a C-terminal regulatory domain (REG) (Fig. Besides acting as a transcription factor, p53 can also translocate to the cytoplasm or mitochondria. p53 then accumulates in the nucleus and turns on expression of target genes, triggering cell-cycle arrest, apoptosis, and DNA-repair processes 20. Under cellular stress, ubiquitylation of p53 is suppressed and p53 is stabilized. p53 protein is normally maintained at low levels in healthy mammalian cells by continuous ubiquitylation and subsequent degradation, mediated by murine double minute 2 (MDM2) E3 ligase. As a transcription factor, p53 is tightly regulated with a short half-life. p53 promotes cell-cycle arrest or apoptosis as a response to cellular stress stimuli, such as oxidative stress, oncogene activation, and DNA damage 20, 21. p53, often referred to as “the guardian of the genome”, is a crucial tumor suppressor mutated in over 50% of human cancer. In EGCG-induced apoptosis and cell growth arrest, p53 was found to play an important role 18, 19. At the molecular level, EGCG has been demonstrated to interact with cancer-related proteins, such as glucose-regulated protein 78 (GRP78) 16 and Ras–GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) 17, with approximately μΜ affinities. In vivo, oral or intravenous administration of green tea or purified EGCG in mice inhibited angiogenesis and restrained solid tumor growth 14, 15. In vitro, EGCG was shown to promote cell growth arrest and induce apoptosis in a variety of human cancer cell lines, including prostate carcinoma cells 9, 10, epidermoid carcinoma cells 11, bladder cancer cells 12, and colon cancer cells 13. found that green tea extract reduced the recurrence rate of colorectal adenomas by 44.2% in a randomized clinical trial in Korea 8. A 10-year prospective study by Nakachi and Imai reported a decreased risk of cancer for those consuming over 10 cups of green tea a day, compared with those consuming below three cups 6, 7. The anti-cancer effect of EGCG has been demonstrated in epidemiological, cell culture, and animal studies, and in clinical trials 5. By drinking cups of green tea or taking an EGCG tablet, a serum concentration of 0.1–1 μM EGCG can be achieved 3, 4. There is 200–300 mg of EGCG in a brewed cup (240 mL) of green tea 2. EGCG accounts for 50–80% of the catechin in green tea. Most of the chemo-preventive effects of green tea on cancer are attributed to polyphenol compounds, among which epigallocatechin-3-gallate (EGCG) is the most important 1. Green tea, a popular beverage consumed worldwide, has been reported to have inhibitory effects against various types of cancer, such as breast, lung, prostate, and colon cancer. Diet-based cancer prevention and therapy have received considerable attention in recent years.
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