# Physiological Effects of Green-Colored Food-Derived Bioactive Compounds on Cancer
## 2 Physiological Effects and Mode of Actions (MoA)
### Chlorophyll  
Chlorophyll is a green pigment present in all plants, cyanobacteria, and algae and is responsible for the photosynthesis process for plants to make their foods. As a component of vegetables and fruits, chlorophyll has been a part of human diet since time immemorial [47]. Chlorophyll has mainly been used as a natural coloring agent, and its bioactive functions have only been discovered in recent years [48]. Chlorophyll is produced and resides in the interior of a cellular structure called chloroplast, and it is primarily composed of a tetrapyrrole ring containing a magnesium ion (Mg\({}^{+}\)) in the center and a hydrophobic chain [49]. While there are five forms of chlorophylls found in nature, only two forms, namely chlorophyll a and chlorophyll b, are widely available in plants and various photosynthetic algae [50]. Both chlorophyll a and b are structurally similar to each other, except for the constitution of a side chain at the C-7 position, where chlorophyll a contains a -CH3 and chlorophyll b contains a CHO group [51]. Based on the polarity of the chlorophyll derivatives, their bioavailability depends on their chemical structure, release, and stability in the gut ambiance and the composition of the food matrix [49; 52]. Therefore, the efficient absorption and metabolism of the lipophilic chlorophylls often require the co-consumption of lipids for their efficient absorption. On the other hand, hydrophilic derivatives, such as chlorophyllides and pheorphoides, would not require any lipid consumption. Although the use of chlorophyll as an anti-carcinogenic agent is a recent phenomenon, the anti-cancer potential of chlorophyll was first mentioned in the 1940s by [PERSON] et al. [53]. Accumulating evidence suggests that chlorophyll and its derivatives can prevent different forms of cancer, including skin, liver, and colorectal cancers in in vitro and in vivo conditions [54]. Chlorophyll is considered one of the essential natural dietary anti-carcinogenic agents for its wide range of biological functions, including antigenotoxic, mutagen engulfing, anti-inflammation, antioxidative, and apoptotic activities [55]. Based on previous studies, the anti-carcinogenic effects of chlorophyll could be attributed to its modulatory actions on CYP1A1 and CYP1B1 expression, cell cycle arrest, cyclin D1, and Bcl-2, DNA adduct formation, and apoptosis [56]. According to a report, chlorophyll can also increase p53, cyclin A and B, and suppress CDK1 and CDK2 in melanoma cells [57]. Chlorophyll has a unique capacity to bind with toxic and carcinogenic substances in the intestinal lumen. Based on this characteristic, a human trial was conducted among the residents in the Qingdong province in China, where the participants were subjected to 100 mg of daily chlorophyll intake for four months [58]. At the end of the trial, a staggering 50% reduction of urinary aflatoxin was found in the subjects. In another study, a group of patients in the Netherlands, under a chlorophyll-deficient diet, experienced a higher incidence of colon cancer [59]. The authors proposed that chlorophyll could be instrumental in blocking the carcinogenic agents in the intestine. Even though chlorophyll has low bioavailability in the lumen, a significant portion of chlorophyll and its derivatives might be active in the intestinal lumen to bind with the mutagens. Although the epidemiological evidence of the chemopre effects of chlorophyll is still inadequate, promising effects of chlorophyll and its synthetic derivatives have been reported in several in vivo cancer models [60]. Chorophyll's anti-cancer potential is making it increasingly popular as a dietary intervention through green or processed foods for cancer prevention. In the EU, chlorophyll and chlorophyls are being used in the formulation of medicines and as a food colorant and bioactive ingredient in different food products to enhance their functionalities [61].