# Physiological Effects of Green-Colored Food-Derived Bioactive Compounds on Cancer
## 2 Physiological Effects and Mode of Actions (MoA)
### Catechin Derivatives  
Catechins are a group of natural flavonoids found in fresh tea leaves, fruits, vegetables, and wine [30]. In total, eight catechins have been identified so far, and among them, only four catechins, such as (-)-Epigallocatechin-3-galactic (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC), are considered highly bioactive for showing numerous health benefits [31]. Green tea is known as the most plentiful source of catechins, where the majority of the catechins (50-80%) is represented by EGCG [32]. Basically, catechins are formed when a 3-carbon chain is attached to two aromatic rings containing several hydroxyl groups [33]. Depending on the arrangement of the hydroxyl groups in the aromatic rings, catechins can be of cis and trans isomers; and each isomer can have two optical isomers, such as (+)-catechin and (-)-catechin [34]. Catechin derivatives, including EGCG, are formed with the esterification of the optical isomers. Notably, due to the presence of hydroxyl groups, catechins can donate hydrogen and bind with water molecules to form larger molecules barring them from being easily absorbed [35]. Therefore, the bioavailability of catechins largely depends on their size and polarity and follows [PERSON]'s Rule of Five [36]. Reportedly, EC with a molecular weight of 290 has remarkably higher bioavailability than the EGCG with a molecular weight of 458. It has been suggested that the significant amount of catechins enter the cells through passive diffusion and later efflux to the intestinal lumen [37; 38]. In the gut, catechins undergo biotransformations, including methylation, glucuronidation, and microbial degradation, before being excreted in the feces [38].  
Green tea and green tea catechins have shown promising efficacies against various forms of cancers, including lung, prostate, ovarian, liver, intestinal, bladder, and skin cancers in cellular and animal cancer models [39]. A formulation of tea catechins, known as Polyphenon E (65% EGCG), remarkably attenuated breast cancer, aberrant crypt foci, and lung adenocarcinoma [37; 39; 40]. In vivo studies have reported that the consumption of green tea could improve malignant cancers, such as stomach, colorectal, liver, and lung cancer [40]. Based on previous findings, multiple molecular mechanisms of how EGCGand other catechins exert anti-cancer effects have been proposed, including the modulation of the inflammatory responses, antioxidant defense, inhibiting angiogenesis, facilitating apoptosis, promoting the tumor suppressor genes, such as p53, arresting the cell cycle, and activating the phase II detoxifying enzymes [41].  
Although the data from the epidemiological studies regarding the effects of green tea and green tea catechins are so far inconclusive, a few of the trials have shown positive results (Table 1). In Japan, patients with colorectal cancer supplemented with 1.5 g green tea extract per day noticeably reduced the recurrence of the tumor cells [42]. Another study in Italy found that the supplementation of 300 mg of green tea catechins could produce substantial effects against prostate cancer [43]. A green tea formulation containing 400 mg of EGCG could significantly reduce the symptoms of chronic lymphocytic leukemis [44]. A cohort study involving 8000 participants with breast cancer showed that the daily intake of green tea resulted in the lower recurrence of the disease [45]. Based on these results, the prospect of EGCG as an anti-cancer agent is worthy of further research attention. Considering its wide-ranging biological activities, including its anti-carcinogenic effects, EGCG is being recommended to be incorporated into functional foods [46].