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Al-Ishaq, R. Phytochemicals and Gastrointestinal Cancer Progression. Encyclopedia. Available online: (accessed on 16 June 2024).
Al-Ishaq R. Phytochemicals and Gastrointestinal Cancer Progression. Encyclopedia. Available at: Accessed June 16, 2024.
Al-Ishaq, Raghad. "Phytochemicals and Gastrointestinal Cancer Progression" Encyclopedia, (accessed June 16, 2024).
Al-Ishaq, R. (2021, June 10). Phytochemicals and Gastrointestinal Cancer Progression. In Encyclopedia.
Al-Ishaq, Raghad. "Phytochemicals and Gastrointestinal Cancer Progression." Encyclopedia. Web. 10 June, 2021.
Phytochemicals and Gastrointestinal Cancer Progression

Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease.The aim of this review is to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/-catenin (wingless-related integration site (Wnt)-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). Overall, phytochemicals improve cancer prognosis through the downregulation of -catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach.

phytochemical gastrointestinal cancer intestinal cancer apoptosis anti-cancerous effects

1. Gastrointestinal Cancer and Phytochemicals

1.1. Gastrointestinal Cancer

Cancer is a leading cause of death worldwide, being responsible for approximately 7.9 million deaths (13% of all deaths) [1]. The rate of cancer-related death is expected to rise to an estimated 12 million deaths by 2030 [2]. Gastrointestinal cancer (GI) is the second most common cause of cancer-related death in the world [3]. Statistical results obtained in 2008 showed that GI cancer is the fourth most common cancer in men and the fifth most common cancer in women [4]. GI cancer is a malignant condition which affects the gastrointestinal tract and accessory organs such as the colon, esophagus, and intestine [5]. The carcinogenesis of GI cancer occurs due to the accumulation of genetic variation of multiple genes such as tumor suppressors, mismatch repair genes, and oncogenes [6]. Imbalance between cellular proliferation and apoptosis leads to the pathogenesis of GI cancer [7]. Internal and external factors such as genetic, obesity, alcohol consumption, and Helicobacter pylori infection contribute to the pathogenesis of GI cancer [8]. Although patients with GI cancer become symptomatic after they have advanced lesions with either local or distant metastasis, commonly presented findings include bloating, epigastric pain, and palpable epigastric mass [9]. Though the incident rate of GI cancer is declining, it remains a major health problem and a huge burden on health care providers [10]. The prognosis of GI cancer is variable between patients depending on its progression at the time of detection. Early detection of GI cancer improves the outcomes of patients. Treatments of the disease include surgery, radiation, and administration of chemotherapy components such as cisplatin, mitomycin, and docetaxel injection [11].

1.2. Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common malignant tumor in the world, with an incidence of 1.2 million new cases and over 600,000 death cases [12]. CRC is the second most common cancer in women and the third most common cancer in men worldwide [10]. As CRC is a so-called westernized disease, the highest incidence rates are found in Australia, New Zealand, North America, and Europe [13]. Although advance treatments are available to improve the survival rate of the disease, CRC remains an incurable disease [14]. While the rate of CRC in adults aged 50 and above decreases, an increase in disease incidence is observed in adults younger than 50 [15]. This suggest that factors such as physical activity, gut microbiome composition, and diet may underline the development of the disease [16]. Like most cancers, CRC is driven by an accumulation of genetic mutations in tumor suppressors such as adenomatous polyposis coli (APC), Smad4 and p53, and oncogenes such as K-ras [17]. These mutagenic accumulations lead to a stepwise progression from normal intestinal epithelial cells to pre-malignant tumor development/adenoma to adenocarcinoma [18]. Etiologically, CRC may be sporadic (more than 80% of cases are sporadic), hereditary, or be related to a history of inflammatory bowel disease [19]. Signs of colon cancer include change in bowel dietary habits and blood in stools [20]. Although treatment of CRC depends on the time of diagnosis and the stage of the disease, common treatments used include surgery, radiation, immunotherapy, and chemotherapy [21].

1.3. Esophageal Cancer

Esophageal cancer is a serious malignancy which accounted for more than 400,000 deaths worldwide in 2005 [22]. Although the incidence rate of other types of cancer is expected to decrease by 2025, the prevalence of esophageal cancer is expected to increase by 140% [23]. The two predominant histological subtypes of esophageal cancer are adenocarcinoma and squamous cell carcinoma, with these having unreliable racial and geographical distribution [24]. Although squamous cell carcinoma remains the most common type of esophageal cancer globally, adenocarcinoma has become the leading type in Western countries due to the higher incidence of obesity and Barrett’s esophagus [25]. Treatment of esophageal cancer includes surgery, radiation, and chemotherapy [26].

1.4. Diet and Microbial Metabolites

The gastrointestinal tract in the human body has the highest population of different microbes, such as in the microbiome. They play a critical role in the well-being of the host [27]. It is estimated that the human gut contains between 30 trillion to 400 trillion micro-organisms [28]. The interaction between the microbiome with different parts of the human gut (mucus layer, epithelial cells, and immune cells) helps in determining the health or disease status of the host [29]. Changes in the gut microbiota due to environmental exposure, host genetics, and diet are known to affect human physiology, prevalence of disease, and nutrition [30]. The gut composition of people lacking Helicobacter pylori infection has identified 128 phylotypes within 8 bacterial phyla of which Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria are the most abundant [31]. Epidemiological studies have indicated that a diet with high fiber and low red meat and fat content reduces the risk of CRC due to the presence of colonic microbiota [32]. They enhance the host’s health by promoting the metabolism of fiber to produce short chain fatty acids (SCFAs) such as butyrate which downregulate pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-12 (IL-12) [33].

2. Anti-Cancerous Effects of Selected Phytochemicals

2.1. Carotenoids

Carotenoids are pigments found in plants, bacteria, algae, and fungi [34]. The family of carotenoids (tetraterpenes) contains 500 compounds, 50 of which exhibit provitamin A activity [35]. While only 40 carotenoids have been identified in the human diet, human blood and tissue contain 20 carotenoids [36]. Carotenoids are well recognized for their antioxidant activities, regulation of cellular growth, immune response, and modulation of gene expression [37]. Pre-dominant carotenoids include lutein, lycopene, and β-carotene, which are abundantly found in egg yolk, tomato, and carrot [38].

2.1.1. Lutein

Lutein in an abundant fat-soluble xanthophyll with a singular molecular formula (C40H56O2) [39]. It is found abundantly in egg yolk, oranges, yellow fruits, and green leafy vegetables [40]. Lutein is one of the two carotenoids that accumulates in fovea in the human retina [41]. It is a major constitute of macular pigment which is responsible for fine feature vision [42]. Recently, lutein has gained public health attention due to its putative role in protection against degenerative eye conditions and cancer [43]. A study performed on a Korean population showed an association between dietary lutein and the risk of colorectal cancer [44]. Lutein has considerable antioxidant function, which regulates apoptosis [45]. Administration of lutein in animal models has been observed to decrease the concentration of K-ras and AKT in tumors, resulting in cell cycle arrest [46]. Mice treated with lutein have been found to significantly inhibit aberrant crypt foci (ACF) development in the colon, reducing cellular proliferation [47]. Additionally, administration of lutein has been observed to reduce β-catenin concentration, hyperplasia, and adenocarcinoma in colonic samples [48]. It also acts as an effective blocking agent by reducing the concentration of specific protein-like β-catenin involved in cellular proliferation and apoptosis (Figure 2) [49]. Moreover, lutein plays a role in reducing reactive oxygen species and oxygen radicals while enhancing DNA damage repair (Table 1) [50].
Figure 2. Phytochemicals as anti-GI cancer agents: mode(s) of action, aberrant signaling pathways (Wnt/β-catenin, detoxification enzymes, cellular apoptosis, PI3K/AKT/mTOR, AMPK, MAPK, and NF-κB), and pathway components targeted by phytochemicals (highlighted in green). Phytochemicals have a wide range of anti-cancerous actions through which one could target multiple mechanisms. These phytochemicals can enhance or suppress (green and red lines, respectively) the mechanisms through several activities. (see text for detailed mode(s) of action for phytochemicals mentioned).

2.1.2. Lycopene

Lycopene is a lipophilic pigment and the main component of-red colored fruits and vegetables such as tomatoes [51]. Lycopene is structurally similar to β-carotene with the molecular formula C50H56, a hydrocarbon chain, and no functional groups [52]. The concentration of lycopene in tomatoes ranges 0.9 to 9.27 mg/g [53]. Lycopene is a potent antioxidant which can counteract reactive oxygen species like peroxyl radicals [54]. The expression of lycopene’s antioxidant activity is due to (i) the detoxification process through the production of enzymes like glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR); (ii) the inhibition of cytochrome P450 2E1, which is critical for the conversion of xenobiotics in cancer; and (iii) the suppression of carcinogen progression (Figure 2) [55]. In addition, lycopene exerts both anti-inflammatory and anti-cancer activity specifically against colorectal cancer [56]. Administration of lycopene using gold nanoparticles as a vehicle has been found to reduce the expression of pro-caspase 3, 8, and 9 and enhance Bcl-2-associated X protein (BAX) expression, thus enhancing the apoptotic pathway [57]. A one-day cultured colon cancer cell with 10 μm of lycopene showed a reduction in cellular growth by reducing the expression of Hmg Co-A reductase and enhancement in Ras translocation from the plasma membrane to cytosol [58]. Lycopene is reported to inhibit the expression of NF-κB and c-Jun N-terminal kinases (JNK), which (i) leads to a decreased tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), and IL-6 and (ii) inhibits the expression of cyclooxygenase 2 (COX-2) and NO production (Table 1) [59]. In a gastric-induced carcinogens model, lycopene has been found to block the activity of carcinogenic cells through the upregulation of a reduced glutathione (GSH) dependent hepatic detoxification system, thus protecting cells from oxidative damage [60].

2.2. Proanthocyanidins

Proanthocyanidins, also known as condensed tannins, result from flavanol condensation [61]. They are abundantly found as polymers and oligomers in fruits, barriers, seeds, leaves, and flowers [62]. Recent interest in proanthocyanidins has been stimulated due to their potential health benefits which arise mainly from their antioxidant activity [63]. The effectiveness of proanthocyanidins are determined by gut microbiome composition [64]. Additionally, they have anticancer properties via the reduction of tumor development by inducing apoptosis or inhibiting cellular proliferation [65].

2.2.1. Quercetin

The cranberry (Vaccinium macrocarpon) is a fruit which has been used as a functional food due to its health benefits [66]. It is a rich source of polyphenols, which exerts anti-inflammatory, antiviral, antibacterial, antioxidant, anticarcinogenic, and antimutagenic activities [67]. It has a complex and rich phytochemical composition, consisting predominantly of A-type procyanidins (PACs), flavan-3-ols, anthocyanins, ursolic acid, quercetin, and benzoic acid [68]. Recently, the cranberry has received attention as a result of its effects related to lowering the risk of cancer [69]. Animal studies have reported the chemoprotective effect of cranberry to suppress the growth of several types of cancer cells, including colon, lung, prostate, oral, and ovarian [70]. Administration of 20% cranberry juice in water to rat models demonstrated a reduction in the total number of ACF [71]. Cranberry extracts have been reported to reduce proinflammatory interleukins and C-reactive protein [72]. APCmin/+ mice fed with 20% (w/w) freeze dried whole cranberry powder for 12 weeks showed a significant prevention of intestinal tumor formation (33.1%) due to induced cellular apoptosis and reduced cellular proliferation [73]. Also, it is reported that cranberry consumption inhibits the activation of the PI3K, AKT, and COX-2 signaling pathway (Table 1) [74]. Administration of cranberries has shown an activation in the AMPK pathway which helped maintain cellular homeostasis [75].

2.2.2. Ellagic Acid

The bilberry (Vaccinium myrtillus L) is a rich natural source of anthocyanins [76]. Total anthocyanin content in the bilberry ranges from 300–700 mg/100 g [77]. It is classified by the American Herbal Products Association as a class 1 herb, which means it can be safely consumed when used appropriately [78]. Ellagic acid is a phenolic compound found in bilberry extracts which has potent antioxidant properties and can chelate metal ions and scavenge free radicals [79]. Treatment of rats’ hepatocyte primary culture with bilberries has shown a protective effect against oxidative damage [80]. Bilberries have been reported to induce phase II xenobiotic detoxification enzymes, which are critical for cancer prevention [81]. Additionally, bilberry-rich extracts have been observed to inhibit the growth of colon cancer cells but to not affect normal colon cells, thus suggesting a possible protective effect against cancer [82]. Rats with genetic colon adenoma fed concentrated bilberry extract (10% w/w) have shown a significant reduction in intestinal adenoma by 15–30% [83]. In a pilot study on 25 patients with colorectal cancer who were given bilberry extract for 7 days, the results showed a significant reduction in tumor cellular proliferation by 7% compared to the results before bilberry administration [84]. Treatment of human monocytic THP-1 cells with bilberry extract showed reduction in pro-inflammatory gene expression, interferon γ (IFN-γ), and cytokine secretion [85]. Moreover, bilberry extract exerts the ability to induce apoptosis and arrest growth in GI cancer (Figure 2) [86]. Bilberry extract has been reported to diminish topoisomerase catalytic activity in colon carcinoma cells, showing a protective DNA effect [87].

2.3. Organosulfur Compounds

Organosulfur compounds are sulfur-containing organic compounds with beneficial anti-inflammatory, antioxidant, and anti-cancerous effects [88]. Animal and epidemiological studies have shown that administration of organosulfur compounds reduces the risk of colorectal cancer through the induction of mitotic arrest and apoptosis [89][90]. Garlic, onion, asparagus, and cruciferous vegetables are abundant in organosulfur compounds.

2.3.1. Allicin

Attention has been given recently to garlic due to its high content of flavonoids and organosulfur compounds like allicin [91]. Worldwide garlic (Allium sativum) has been frequently used as a dietary botanical supplement [92]. Ally sulfur compounds like allicin found in garlic (1% of garlic’s dye weight) seems to be responsible for the beneficial effects of garlic [93]. Animal studies have shown that administration of garlic reduces the formation of ACF [94]. The mechanisms by which garlic inhibits the growth of carcinogen cells include reduction of DNA adducts, regulation of cellular arrest, activation of metabolizing detoxification enzymes, and induction of differentiation and apoptosis [95][96]. Organosulfur compounds present in garlic have shown potential for an anti-cancer drug by the modulation of epithelial growth factor receptor (EGFR), which plays a role in cell division [97]. Results obtained from an induced colitis mouse model have shown that administration of diallyl disulfide extracted from garlic is able to prevent the development of colitis-induced colorectal cancer [98]. In addition, garlic has been observed to prevent prolonged inflammation in mice, which supports the chemoprotective effect of garlic in CRC [99]. Moreover, consumption of garlic suppresses the activity of NF-κB by inhibiting phosphorylated P65 translocation (Figure 2) [100]. In xenograft nude mice, administration of S-allylmercaptocysteine (SAMC) in combination with rapamycin (a macrolide compound) was found to enhance anticancer ability by suppressing tumor growth and inducing apoptosis (Table 1) [101]. Administration of aged garlic extract in rat tumor models has been shown to attenuate colon tumor progression effectively by reducing cellular proliferation through the attenuation of NF-κB activity [102]. A meta-analysis study has indicated that the consumption of garlic is associated with reduced gastric cancer with a 95% confidence interval and a 0.53 odd ratio [103].

2.3.2. Allyl Propyl Disulfide

Chemical groups found in onions such as flavonoids, alk(en)yl cysteine sulfoxides (ACSOs), and allyl propyl disulfide are associated with the health benefits of onions [104]. The consumption rate of onion (Allium cepa L.) has increased worldwide, leading to an increase in the national production of onion by 25% over the last decade [105]. Compounds from onions have been reported to have multiple health benefits, including having antiplatelet, anticarcinogenic, and antithrombogenic activities [106]. Onion extracts have been reported to significantly induce apoptosis and reduce cellular proliferation in colorectal cancer [107]. An in vivo study has indicated that administration of onion in a hyperlipidemic colorectal cancer model plays a similar role to capecitabine in a colorectal cancer model without hyperlipidemia by inhibiting CRC and reducing hyperlipidemia [108]. Human cancer adenocarcinoma cells treated with 200 μm Se-methyl-L-selenocysteine (MSeC) for 24 h have been found to trigger 80% apoptosis in cells through endoplasmic reticulum stress rather than reactive oxygen species stress (Table 1) [109]. The benefit of onions is not limited to reducing or treating GI cancer but also to detecting cancer. One study used carbon nano onion films to develop a capacitive immunosensor for a CA19-9 cancer biomarker detector which succeeded in detecting CA19-9 in whole lysate colorectal adenocarcinoma using the sensor combined with information visualization methods [110].

2.3.3. Asparagusic Acid

Asparagus species are native medical shrubs which have beneficial medical properties and which belong to the Liliaceae family [111]. Major bioactive compounds found in asparagus include steroidal saponins, asparagusic acid, vitamins (A, B1, B2, C, E, Mg, P, Ca, and Fe), folic acid, asparagine, tyrosine, arginine, essential oils, tannin, resin, and flavonoids. The health properties of asparagus include anti-microbial, antioxidant, and cytotoxic activities [112]. Asparagus extracts have illustrated a potent cytotoxic effect against colorectal cancer [113]. Treatment of Myeloid-derived suppressor cells (MDSCs) with asparagus polysaccharide have shown a significant increase in apoptosis through intrinsic pathways and a significant decrease in cellular proliferation [114]. Old stems of asparagus (SSA) tested on colon cancer cells have been found to suppress cellular viability and block cellular migration and invasion through Rho GTPase signaling pathway modulation [115]. In human colon adenocarcinoma, methanolic extracts from white asparagus have demonstrated TRAIL death receptor pathway activation leading to the activation of caspase-8 and caspase-3, and, finally, to cell death. In addition, asparagus extracts have been seen to inhibit cellular pro-inflammatory mediators like MMP7, MMP9, and TNF-α [116].

2.3.4. Sulforaphane

Cruciferous vegetables refer to those which belong to the Brassicaceae family and include cabbage, broccoli, and Brussel sprouts [117]. This family is known for the glucosinolate, a sulfur-containing compound synthesized endogenously in plants derived from amino acid and glucose residues [118]. Upon cellular rupture through vegetable consumption, glucosinolates are hydrolyzed by endogenous enzymes and produce potential compounds such as thiocyanates and nitriles [119]. Cruciferous vegetables contain several phytochemical compounds such as sulforaphane. Studies have shown the beneficial effects of cruciferous vegetables which have helped inhibit the development of GI cancer [120]. In vivo and in vitro studies have demonstrated the ability of cruciferous vegetables to defend healthy cells against radiation and chemically-induced carcinogenesis [121]. Additionally, these vegetables have been shown to inhibit cellular proliferation, migration, and survival of tumor cells [122]. Cruciferous vegetables demonstrate antioxidant activity as they widely show a protective effect against oxidative stress through the depletion of glutathione [123]. Additionally, these vegetables induce acute oxidative stress through the inhibition of P38 MAPK, which inhibits Nrf2-Keap 1 dissociation (Table 1) [124]. Cruciferous vegetables guard against colorectal cancer through several mechanisms: (i) the modulation of detoxification enzymes (Figure 2), (ii) the induction of cellular apoptosis, and (iii) the controlling of cancer cellular growth through cell cycle arrest [125][126][127]. A meta-analysis study has shown that cruciferous vegetables significantly reduce the risk of gastric and colorectal cancer by 19% and 8%, respectively [128].
Table 1. Representive Phytochemicals and Their Underlying Anti-Cancerous Effects.
Phytochemical Subclass Phytochemical and Structure Dietary Source Conversion Reaction Metabolites Produced Mechanism of Action Model Used References
In Vivo In Vitro
Carotenoids Lutein
Biomolecules 10 00105 i001
Egg yolk, kale, spinach, parsley, and peas Oxidation 3′-dehydro-lutein
Reduces slightly the risk of colorectal cancer
Reduces the risk of colorectal neoplasms in women
Inhibits the growth of carcinoma cells
Decreases the concentration of AKT expression which reduces cellular proliferation
Decreases β-catenin concentration thus enhancing the apoptotic pathway
Regulates miRNA expression through DICER 1 activity
Enhances DNA damage repair
Induces humoral and cell mediated-immune response
Scavenges against oxygen radicals
Quenches reactive oxygen species
Activates MAPK pathway through MAP3K9 interaction
Protects against the formation of colonic aberrant crypt foci
Sprague-Dawley rats.
Human normal colon epithelial cells
Human colon adenocarcinoma cells
Biomolecules 10 00105 i002
Tomato, guava, papaya, grapefruit, and watermelon Auto-oxidation Radical-mediated oxidation Apo-10′-lycopenoids
Suppresses the progression of carcinogenesis through the inhibition of DNA synthesis
Inhibits cell invasion, metastasis, and angiogenesis
Reduces cell migration capacity
Downregulates AKT, NF-κB, MMP-2, MMP-7, and MMP-9
Decreases β-catenin concentration
Reduces pro-inflammatory mediators and enzymes such as TNF-a and COX-2, respectively
Prevents oxidative damage through scavenging oxygen free radicals
Suppresses the expression of cyclin D1 and PCNA proteins
Inhibits the formation of colonic ACFs
Stimulates the activity of enzymes such as glutathione reductase, glutathione peroxidase, and glutathione S-transferase
Enhances apoptotic pathway
Activates MAPK signaling gene
Upregulates p21 cell cycle inhibitor protein
Induced-colitis rat models
Sprague-Dawely rats
Fischer 344/NSIc rats
HT-29 cell lines
Biomolecules 10 00105 i003
Carrot Oxidation Falcarindiol 6-methoxymellein
Inhibits the formation of neoplastic tumors
Reduces the number of polyps in the colon
Inhibits pleiotropic cytokines and the NF-κB pathway
Reduces the formation of macroscopic neoplasms by targeting low abundant gut microbiome
Inhibits cellular proliferation through MAPK/ERK and PI3K/AKT pathway inhibition
Enhances p53-dependent apoptosis pathway
Azoxymethane (AOM) treated rats
HT-29 cells
HCT 116 cells
CCD-33Co cells
Pro-anthocy-anidins Quercetin
Biomolecules 10 00105 i004
Cranberry Sulfation Conjugation 3-(4hydroxyphenyl) -propionic acid hippuric acid catechol-O-sulfate
Reduces small intestine tumor formation
Reduces inflammatory responses when consumed with fiber
Reduces tumor incidence, multiplicity, burden, and average tumor volume
Reduces colonic inflammatory cytokine expression such as IFN-γ and TNF-α
Inhibits the activation of the PI3K, AKT, and COX-2 signaling pathway
Inhibits cancer cell proliferation and tumor growth
Inhibits VEGF, MMP-2, and MMP-9 expression
Inhibits the incidence of AOM-induced ACF
Induces cellular apoptosis
Increases the number of colonic goblet cells and MUC 2 production
Increases caecal short fatty acids concentration
Apc(min/+) mice
Male weanling rats
HCT116 cell lines
HT-29 cell lines
Cancer cell line encyclopedia (CCLE)
Ellagic Acid
Biomolecules 10 00105 i005
Bilberry Glucuronidation
Reduces the expression of proinflammatory cytokines
Reduces inflammation and tumor development
Inhibits cellular proliferation
Inhibits the formation of colonic ACFs
Suppresses the activity of topoisomerase I and II which reduces DNA damage
Induces cellular apoptosis through NF-κB inhibition
Protective activities against colorectal cancer
Female Balb/c mice
Intraepithelial neoplasia
HCT-116 cell line
Organosulfur Compounds Allicin
Biomolecules 10 00105 i006
Garlic Oxidation Hydrolysis Allyl methyl sulfide (AMS) Allyl methyl sulfoxide (AMSO) Allyl methyl sulfone (AMSO2)
Inactivates NF-κB localization by inhibiting glycogen synthase kinase 3 (GSK-3) which prevent colitis-induced colorectal cancer
Suppresses cellular proliferation and tumor growth
Induces colon cancer cell apoptosis
Anticancer activity against colorectal cancer through the modulation of epithelial growth factor receptor (EGFR)
Activates antioxidative transcriptor Nrf2
Xenograft nude mice
HCT-116 cell line
Allyl propyl disulfide
Biomolecules 10 00105 i007
Onion Reduction Quercetin 3,4‘-diglucoside Quercetin 4‘-glucoside
Reduces cellular proliferation
Reduces migration rate of cancer cells
Reduces tumor growth rate in colorectal cancer
Induces cellular apoptosis
Induces cell cycle arrest at G2/M phase
Caco-2 cell line
SW620 cell line
Asparagusic acid
Biomolecules 10 00105 i008
Asparagus Sulfation Asparagus polysaccharide dimethyl sulfide
Cytotoxic effect against human colon cancer cell greater than 5-FU
Reduces cellular proliferation
Inhibits cell motility and cellular growth by targeting Rho GTPase signaling pathway
Induces intrinsic apoptosis through toll-like receptor 4
Enhances the expression of BAX and Caspase 9
HCT-116 cell line
Caco-2 cell line
Biomolecules 10 00105 i009
Broccoli, cabbage, Brussels sprout, and cauliflower Hydrolysis Thiocyanates Isothiocyanates Epithionitrile nitrile
Reduces the risk of adenomatous polyps
Prevents colorectal cancer through miRNA modulation
Protects against Barrett’s esophagus
Induces apoptosis and cellular arrest
Induces detoxification enzymes
Cytoprotective effect through the induction of Nrf2
Scavenges against free radicals
Squamous cell carcinoma
Other Phytochemicals Pectin
Biomolecules 10 00105 i010
Apples, plums, oranges, and gooseberries Colonic fermentation Butyrate
Inhibits cancer cell metastasis of gastrointestinal cancer
Inhibits colon cancer cell proliferation by downregulating ICAM1 expression
Induces apoptosis by downregulating Bcl-xL and Cyclin B
Modulates the expression of signature miRNA
Delivers oral drugs for colon cancer treatment
BALB/c mice
HCT116 cells
Caco-2 cell line
Biomolecules 10 00105 i011
Ginger Hydrolysis Curcumin glucuronide Curcumin sulfate
Suppresses tumor growth by suppressing PPARγ pathway
Prevents cellular proliferation
Induces cellular apoptosis
Upregulates the expression of Caspase-3, cytochrome C, and BAX
Cancer stem-like cells (CSC)
p-Couramic acid
Biomolecules 10 00105 i012
Navy beans Hydrolysis N-methylpipecolate
Reduces oxidative stress
Reduces the number of colonic aberrant cypt foci
Anti-tumor activity against colorectal cancer
Increases the abundance of amino acids, phytochemicals, and lipids in stool
Induces cellular apoptosis
FVB/N mice
Ferulic acid
Biomolecules 10 00105 i013
Rice bran Colonic fermentation Tryptophan
Inhibits cellular proliferation, cell cycle progression, and tumor growth
Decreases β-catenin and COX-2 in colon tumors
Increases the production of SCFAs
Induces nitric oxide synthase expression, Caspase-3 activation, and NF-κB pathway
Induces cellular apoptosis and lipid peroxidation
Scavenges free radicals
Modifies the composition of intestinal microbiota
APC (min) mice
Caco-2 cells
HAT-29 cells


  1. Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin. 2011, 61, 69–90.
  2. National Cancer Institute. Gastric cancer treatment PDQ. Available online: (accessed on 8 July 2010).
  3. Derakhshan, M.H.; Yazdanbod, A.; Sadjadi, A.R.; Shokoohi, B.; McColl, K.E.; Malekzadeh, R. High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran. Gut 2004, 53, 1262–1266.
  4. Zali, H.; Rezaei-Tavirani, M.; Azodi, M. Gastric cancer: Prevention, risk factors and treatment. Gastroenterol. Hepatol. Bed Bench. 2011, 4, 175–185.
  5. Sitarz, R.; Skierucha, M.; Mielko, J.; Offerhaus, G.J.A.; Maciejewski, R.; Polkowski, W.P. Gastric cancer: Epidemiology, prevention, classification, and treatment. Cancer Manag. Res. 2018, 10, 239–248.
  6. Holian, O.; Wahid, S.; Atten, M.J.; Attar, B.M. Inhibition of gastric cancer cell proliferation by resveratrol: Role of nitric oxide. Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 282, G809–G816.
  7. Zhou, X.M.; Wong, B.C.; Fan, X.M.; Zhang, H.B.; Lin, M.C.; Kung, H.F.; Lam, S.K. Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. Carcinogenesis 2011, 22, 1393–1397.
  8. Hundahl, S.A.; Phillips, J.L.; Menck, H.R. The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer 2000, 88, 921–932.
  9. Correa, P. Gastric cancer: Overview. Gastroenterol. Clin. North. Am. 2013, 211–217.
  10. Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015, 136, E359–E386.
  11. Zali, H.; Rezaei-Tavirani, M.; Kariminia, A.; Yousefi, R.; Shokrgozar, M.A. Evaluation of growth inhibitory and apoptosis inducing activity of human calprotectin on the human gastric cell line (AGS). Iran. Biomed. J. 2008, 12, 7–14.
  12. Li, Y.H.; Niu, Y.B.; Sun, Y.; Zhang, F.; Liu, C.X.; Fan, L.; Mei, Q.B. Role of phytochemicals in colorectal cancer prevention. World J. Gastroenterol. 2015, 21, 9262–9272.
  13. Perdue, D.G.; Haverkamp, D.; Perkins, C.; Daley, C.M.; Provost, E. Geographic variation in colorectal cancer incidence and mortality, age of onset, and stage at diagnosis among American Indian and Alaska Native people, 1990–2009. Am. J. Public Health 2014, 104, S404–S414.
  14. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018, GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424.
  15. Siegel, R.L.; Fedewa, S.A.; Anderson, W.F.; Miller, K.D.; Ma, J.; Rosenberg, P.S.; Jemal, A. Colorectal Cancer Incidence Patterns in the United States, 1974–2013. J. Natl. Cancer Inst. 2017, 109.
  16. Siegel, R.L.; Miller, K.D.; Fedewa, S.A.; Ahnen, D.J.; Meester, R.G.S.; Barzi, A.; Jemal, A. Colorectal cancer statistics. CA Cancer J. Clin. 2017, 67, 177–193.
  17. Tomasetti, C.; Marchionni, L.; Nowak, M.A.; Parmigiani, G.; Vogelstein, B. Only three driver gene mutations are required for the development of lung and colorectal cancers. Proc. Natl. Acad. Sci. USA 2015, 112, 118–123.
  18. Li, Y.; Zhang, T.; Chen, G.Y. Flavonoids and Colorectal Cancer Prevention. Antioxid 2018, 7, 187.
  19. Zhao, Y.; Hu, X.; Zuo, X.; Wang, M. Chemopreventive effects of some popular phytochemicals on human colon cancer: A review. Food Funct. 2018, 9, 4548–4568.
  20. Marmol, I.; Sanchez-de-Diego, C.; Pradilla Dieste, A.; Cerrada, E.; Rodriguez Yoldi, M.J. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int. J. Mol. Sci. 2017, 18, 197.
  21. Kuipers, E.J.; Grady, W.M.; Lieberman, D.; Seufferlein, T.; Sung, J.J.; Boelens, P.G.; Watanabe, T. Colorectal cancer. Nat. Rev. Dis. Primers. 2015, 1, 15065.
  22. Lambert, R.; Hainaut, P. The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer. Best Pr. Res. Clin. Gastroenterol. 2007, 21, 921–945.
  23. Herszenyi, L.; Tulassay, Z. Epidemiology of gastrointestinal and liver tumors. Eur. Rev. Med. Pharm. Sci. 2010, 14, 249–258.
  24. Hongo, M.; Nagasaki, Y.; Shoji, T. Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity. J. Gastroenterol. Hepatol. 2009, 24, 729–735.
  25. Kubo, A.; Corley, D.A. Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States. Am. J. Gastroenterol. 2004, 99, 582–588.
  26. Haidry, R.J.; Butt, M.A.; Dunn, J.M.; Gupta, A.; Lipman, G.; Smart, H.L.; Registry, U.R. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett’s oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry. Gut 2015, 64, 1192–1199.
  27. Hooper, L.V.; Macpherson, A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 2010, 10, 159–169.
  28. Mokili, J.L.; Rohwer, F.; Dutilh, B.E. Metagenomics and future perspectives in virus discovery. Curr. Opin Virol. 2012, 2, 63–77.
  29. Ursell, L.K.; Haiser, H.J.; Van Treuren, W.; Garg, N.; Reddivari, L.; Vanamala, J.; Knight, R. The intestinal metabolome: An intersection between microbiota and host. Gastroenterology 2014, 146, 1470–1476.
  30. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The human microbiome project. Nature 2007, 449, 804–810.
  31. Cho, I.; Blaser, M.J. The human microbiome: At the interface of health and disease. Nat. Rev. Genet. 2012, 13, 260–270.
  32. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252.
  33. Wroblewski, L.E.; Peek, R.M.Jr.; Coburn, L.A. The Role of the Microbiome in Gastrointestinal Cancer. Gastroenterol. Clin. North. Am. 2016, 45, 543–556.
  34. Slattery, M.L.; Benson, J.; Curtin, K.; Ma, K.N.; Schaeffer, D.; Potter, J.D. Carotenoids and colon cancer. Am. J. Clin. Nutr. 2000, 71, 575–582.
  35. Palozza, P.; Calviello, G.; Serini, S.; Maggiano, N.; Lanza, P.; Ranelletti, F.O.; Bartoli, G.M. Beta-carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells. Free Radic. Biol. Med. 2001, 30, 1000–1100.
  36. Milani, A.; Basirnejad, M.; Shahbazi, S.; Bolhassani, A. Carotenoids: Biochemistry, pharmacology and treatment. Br. J. Pharmacol. 2017, 174, 1290–1324.
  37. Malila, N.; Virtamo, J.; Virtanen, M.; Pietinen, P.; Albanes, D.; Teppo, L. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. Eur. J. Clin. Nutr. 2002, 56, 615–621.
  38. Smith-Warner, S.A.; Elmer, P.J.; Tharp, T.M.; Fosdick, L.; Randall, B.; Gross, M.; Potter, J.D. Increasing vegetable and fruit intake: Randomized intervention and monitoring in an at-risk population. Cancer Epidemiol. Biomark. Prev. 2000, 9, 307–317.
  39. Lim, L.S.; Mitchell, P.; Seddon, J.M.; Holz, F.G.; Wong, T.Y. Age-related macular degeneration. Lancet 2012, 379, 1728–1738.
  40. Perry, A.; Rasmussen, H.; Johnson, E.J. Xanthophyll (lutein, zeaxanthin) content in fruits, vegetables and corn and egg products. J. Food Compos. Anal. 2009, 22, 9–15.
  41. Ohnson, E.J. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr. Rev. 2014, 72, 605–612.
  42. Akuffo, K.O.; Nolan, J.; Stack, J.; Moran, R.; Feeney, J.; Kenny, R.A.; Peto, T.; Dooley, C.; O’Halloran, A.M.; Cronin, H. Prevalence of age-related macular degeneration in the Republic of Ireland. Br. J. Ophthalmol. 2015, 99, 1037–1044.
  43. Ranard, K.M.; Jeon, S.; Mohn, E.S.; Griffiths, J.C.; Johnson, E.J.; Erdman, J.W.J.r. Dietary guidance for lutein: Consideration for intake recommendations is scientifically supported. Eur. J. Nutr. 2017, 56, 37–42.
  44. Kim, J.; Lee, J.; Oh, J.; Chang, H.J.; Sohn, D.; Kwon, O.; Shin, A.; Kim, J. Dietary Lutein Plus Zeaxanthin Intake and DICER1 rs3742330 A > G Polymorphism Relative to Colorectal Cancer Risk. Sci. Rep. 2019, 9, 3406.
  45. Collins, A.R.; Harrington, V. Antioxidants; not the only reason to eat fruit and vegetables. Phytochem. Rev. 2003, 1, 167–174.
  46. Femia, A.P.; Tarquini, E.; Salvadori, M.; Ferri, S.; Giannini, A. K-ras mutations and mucin profile in preneoplastic lesions and colon tumors induced in rats by 1,2-dimethylhydrazine. Int. J. Cancer 2008, 1, 117–123.
  47. Gali-Muhtasib, H.U.; Younes, I.H.; Karchesy, J.J.; el-Sabban, M.E. Plant tannins inhibit the induction of aberrant crypt foci and colonic tumors by 1,2-dimethylhydrazine in mice. Nutr. Cancer 2001, 39, 108–116.
  48. Reynoso-Camacho, R.; González-Jasso, E.; Ferriz-Martínez, R.; Villalón-Corona, B.; Salgado, L.; Ramos-Gómez, M. Dietary Supplementation of Lutein Reduces Colon Carcinogenesis in DMH-Treated Rats by Modulating K-ras, PKB, and β-catenin Proteins. Nutr. Cancer 2010, 63, 39–45.
  49. Satia-Abouta, J.; Galanko, J.A.; Martin, C.F.; Potter, J.D.; Ammerman, A.; Sandler, R.S. Associations of micronutrients with colon cancer risk in African Americans and whites: Results from the North Carolina Colon Cancer Study. Cancer Epidemiol. Biomark. Prev. 2003, 12, 747–754.
  50. Santocono, M.; Zurria, M.; Berrettini, M.; Fedeli, D.; Falcioni, G. Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA-irradiated cells. J. Photochem. Photobiol. B 2006, 85, 205–215.
  51. Trejo-Solís, C.; Pedraza-Chaverrí, J.; Torres-Ramos, M. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid. Based Complement. Alternat. Med. 2013, 2013, 705121.
  52. Story, E.N.; Kopec, R.E.; Schwartz, S.J.; Harris, G.K. An update on the health effects of tomato lycopene. Annu. Rev. Food Sci. Technol. 2010, 1, 189–210.
  53. Bandeira, A.C.; da Silva, T.P.; de Araujo, G.R. Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice. Chem. Biol. Interact. 2016, 263, 7–17.
  54. Boehm, F.; Edge, R.; Truscott, T.G.; Witt, C. A dramatic effect of oxygen on protection of human cells against γ-radiation by lycopene. FEBS Lett. 2016, 590, 1086–1093.
  55. Slattery, M.L.; Lundgreen, A.; Welbourn, B.; Wollf, R.K.; Corcoran, C. Oxidative balance and colon and rectal cancer: Interaction of lifestyle factors and genes. Mutat. Res. 2012, 734, 30–40.
  56. Youn, S.W. Systemic inflammatory response as a prognostic factor in patients with cancer. J. Korean Orient Oncol. 2012, 17, 1–7.
  57. Lin, M.C.; Wang, F.Y.; Kuo, Y.H.; Tang, F.Y. Cancer chemopreventive effects of lycopene: Suppression of MMP-7 expression and cell invasion in human colon cancer cells. J. Agric. Food Chem. 2011, 59, 11304–11318.
  58. Palozza, P.; Colangelo, M.; Simone, R. Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 2010, 31, 1813–1821.
  59. Cha, J.H.; Kim, W.K.; Ha, A.W.; Kim, M.H.; Chang, M.J. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells. Nutr. Res. Pract. 2017, 11, 90–96.
  60. Bhuvaneswari, V.; Velmurugan, B.; Nagini, S. Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutr. Res. 2001, 8, 1117–1124.
  61. De la Iglesia, R.; Milagro, F.I.; Campion, J.; Boque, N.; Martinez, J.A. Healthy properties of proanthocyanidins. Biofactors 2010, 36, 159–168.
  62. Blade, C.; Aragones, G.; Arola-Arnal, A.; Muguerza, B.; Bravo, F.I.; Salvado, M.J.; Suarez, M. Proanthocyanidins in health and disease. Biofactors 2016, 42, 5–12.
  63. Cos, P.; De Bruyne, T.; Hermans, N.; Apers, S.; Berghe, D.V.; Vlietinck, A.J. Proanthocyanidins in health care: Current and new trends. Curr. Med. Chem. 2004, 11, 1345–1359.
  64. Casanova-Marti, A.; Serrano, J.; Portune, K.J.; Sanz, Y.; Blay, M.T.; Terra, X.; Pinent, M. Grape seed proanthocyanidins influence gut microbiota and enteroendocrine secretions in female rats. Food Funct. 2018, 9, 1672–1682.
  65. Lee, Y. Cancer Chemopreventive Potential of Procyanidin. Toxicol. Res. 2017, 33, 273–282.
  66. Neto, C.C. Cranberries: Ripe for more cancer research? J. Sci. Food Agric. 2011, 91, 2303–2307.
  67. Côté, J.; Caillet, S.; Doyon, G.; Sylvain, J.F.; Lacroix, M. Bioactive compounds in cranberries and their biological properties. Crit. Rev. Food Sci. Nutr. 2010, 50, 666–679.
  68. Pappas, E.; Schaich, K.M. Phytochemicals of cranberries and cranberry products: Characterization, potential health effects, and processing stability. Crit. Rev. Food Sci. Nutr. 2009, 49, 741–781.
  69. Duthie, S.J.; Jenkinson, A.M.; Crozier, A.; Mullen, W.; Pirie, L.; Kyle, J.; Yap, L.S.; Christen, P.; Duthie, G.G. The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. Eur. J. Nutr. 2006, 45, 113–122.
  70. Wu, X.; Song, M.; Cai, X.; Neto, C.; Tata, A.; Han, Y.; Xiao, H. Chemopreventive Effects of Whole Cranberry (Vaccinium macrocarpon) on Colitis-Associated Colon Tumorigenesis. Mol. Nutr. Food Res. 2018, 62, e1800942.
  71. Boateng, J.; Verghese, M.; Shackelford, L.; Walker, L.T.; Khatiwada, J.; Ogutu, S.; Chawan, C.B. Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Food Chem. Toxicol. 2007, 45, 725–732.
  72. Xiao, S.D.; Shi, T. Is cranberry juice effective in the treatment and prevention of Helicobacter pyloriinfection of mice? Chin. J. Dig. Dis. 2003, 4, 136–139.
  73. Jin, D.; Liu, T.; Dong, W.; Zhang, Y.; Wang, S.; Xie, R.; Cao, H. Dietary feeding of freeze-dried whole cranberry inhibits intestinal tumor development in Apc(min/+) mice. Oncotarget 2017, 8, 97787–97800.
  74. Koosha, S.; Alshawsh, M.A.; Looi, C.Y.; Seyedan, A.; Mohamed, Z. An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer. Int. J. Med. Sci. 2016, 13, 374–385.
  75. Sun, Q.; Yue, Y.; Shen, P.; Yang, J.J.; Park, Y. Cranberry Product Decreases Fat Accumulation in Caenorhabditis elegans. J. Med. Food. 2016, 19, 427–433.
  76. Upton, R. Bilberry Fruit Vaccinium myrtillus L. Standards of Analysis, Quality Control, and Therapeutics; AHP: Santa Cruz, CA, USA, 2001.
  77. Chu, W.; Cheung, S.C.M.; Lau, R.A.W.; Benzie, I.F.F. Bilberry (Vaccinium myrtillus L.). In Herbal Medicine: Biomolecular and Clinical Aspects; Benzie, I.F.F., Wachtel-Galor, Sissi, Eds.; CRC Press: Boca Raton, FL, USA, 2011.
  78. Mazza, G.; Kay, C.D.; Correll, T.; Holub, B.J. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J. Agric. Food Chem. 2002, 50, 7731–7737.
  79. Valentova, K.; Ulrichova, J.; Cvak, L.; Simanek, V. Cytoprotective effect of a bilberry extract against oxidative damage of rat hepatocytes. Food Chem. 2006, 101, 912–917.
  80. Hodges, R.E.; Minich, D.M. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J. Nutr. Metab. 2015, 760689.
  81. Lala, G.; Malik, M.; Zhao, C.; He, J.; Kwon, Y.; Giusti, M.M.; Magnuson, B.A. Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutr. Cancer 2006, 54, 84–93.
  82. Mutanen, M.; Pajari, A.M.; Paivarinta, E.; Misikangas, M.; Rajakangas, J.; Marttinen, M.; Oikarinen, S. Berries as preventive dietary constituents-a mechanistic approach with ApcMin+ mouse. Asia Pac. J. Clin. Nutr. 2008, 17, 123–125.
  83. Wang, L.S.; Stoner, G.D. Anthocyanins and their role in cancer prevention. Cancer Lett. 2008, 269, 281–290.
  84. Lippert, E.; Ruemmele, P.; Obermeier, F.; Goelder, S.; Kunst, C.; Rogler, G.; Endlicher, E. Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model. Digestion 2017, 95, 275–280.
  85. Thomasset, S.; Berry, D.P.; Cai, H.; West, K.; Marczylo, T.H.; Marsden, D.; Gescher, A.J. Pilot study of oral anthocyanins for colorectal cancer chemoprevention. Cancer Prev. Res. Phila 2009, 2, 625–633.
  86. Esselen, M.; Fritz, J.; Hutter, M.; Teller, N.; Baechler, S.; Boettler, U.; Marko, D. Anthocyanin-rich extracts suppress the DNA-damaging effects of topoisomerase poisons in human colon cancer cells. Mol. Nutr. Food Res. 2011, 55, S143–S153.
  87. Chau, I.; Cunningham, D. Adjuvant therapy in colon cancer—what, when and how? Ann. Oncol. 2006, 17, 1347–1359.
  88. Xiao, D.; Pinto, J.T.; Gundersen, G.G.; Weinstein, I.B. Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells. Mol. Cancer Ther. 2005, 4, 1388–1398.
  89. Moriarty, R.M.; Naithani, R.; Surve, B. Organosulfur compounds in cancer chemoprevention. Mini. Rev. Med. Chem. 2007, 7, 827–838.
  90. Nagini, S. Cancer chemoprevention by garlic and its organosulfur compounds-panacea or promise? Anticancer Agents Med. Chem. 2008, 8, 313–321.
  91. El-Bayoumy, K.; Sinha, R.; Pinto, J.T. Cancer chemoprevention by garlic and garlic-containing sulfur and selenium compounds. J. Nutr. 2016, 136, S864–S869.
  92. Hu, J.Y.; Hu, Y.W.; Zhou, J.J.; Zhang, M.W.; Li, D.; Zheng, S. Consumption of garlic and risk of colorectal cancer: An updated meta-analysis of prospective studies. World J. Gastroenterol. 2014, 20, 15413–15422.
  93. Ross, S.A.; Finley, J.W.; Milner, J.A. Allyl sulfur compounds from garlic modulate aberrant crypt formation. J. Nutr. 2006, 136, S852–S854.
  94. Powolny, A.A.; Singh, S.V. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related allium vegetable-derived organosulfur compounds. Cancer Lett. 2008, 269, 305–314.
  95. Yi, L.; Su, Q. Molecular mechanisms for the anticancer effects of diallyl disulfide. Food Chem. Toxicol. 2013, 57, 362–370.
  96. Roy, N.; Nazeem, P.A.; Babu, T.D.; Abida, P.S.; Narayanankutty, A.; Valsalan, R.; Raghavamenon, A.C. EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide. Interdiscip Sci. 2008, 10, 686–693.
  97. Saud, S.M.; Li, W.; Gray, Z.; Matter, M.S.; Colburn, N.H.; Young, M.R.; Kim, Y.S. Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-kappaB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3beta. Cancer Prev. Res. Phila 2016, 9, 607–615.
  98. Janakiram, N.B.; Rao, C.V. The role of inflammation in colon cancer. Advances in Experimental Medicine and Biology; Springer: Berlin, Germany, 2014; Volume 816, pp. 25–52.
  99. Erstad, D.J.; Cusack, J.C. Targeting the NF-kappaB pathway in cancer therapy. Surg. Oncol. Clin. N. Am. 2013, 22, 705–746.
  100. Li, S.; Yang, G.; Zhu, X.; Cheng, L.; Sun, Y.; Zhao, Z. Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncol. Rep. 2017, 38, 1637–1644.
  101. Raghu, R.; Lu, K.H.; Sheen, L.Y. Recent Research Progress on Garlic (da suan) as a Potential Anticarcinogenic Agent Against Major Digestive Cancers. J. Tradit. Complement Med. 2012, 2, 192–201.
  102. Zhou, Y.; Zhuang, W.; Hu, W.; Liu, G.J.; Wu, T.X.; Wu, X.T. Consumption of large amounts of Allium vegetables reduces risk for gastric cancer in a meta-analysis. Gastroenterology 2011, 141, 80–89.
  103. Griffiths, G.; Trueman, L.; Crowther, T.; Thomas, B.; Smith, B. Onions--a global benefit to health. Phytother. Res. 2002, 16, 603–615.
  104. Suleria, H.A.; Butt, M.S.; Anjum, F.M.; Saeed, F.; Khalid, N. Onion: Nature protection against physiological threats. Crit. Rev. Food Sci. Nutr. 2015, 55, 50–66.
  105. Izzo, A.A.; Capasso, R.; Capasso, F. Eating garlic and onion: A matter of life or death. Br. J. Cancer 2004, 91, 194.
  106. Murayyan, A.I.; Manohar, C.M.; Hayward, G.; Neethirajan, S. Antiproliferative activity of Ontario grown onions against colorectal adenocarcinoma cells. Food Res. Int. 2017, 96, 12–18.
  107. He, Y.; Jin, H.; Gong, W.; Zhang, C.; Zhou, A. Effect of onion flavonoids on colorectal cancer with hyperlipidemia: An in vivo study. Onco Targets Ther. 2014, 7, 101–110.
  108. Tung, Y.C.; Tsai, M.L.; Kuo, F.L.; Lai, C.S.; Badmaev, V.; Ho, C.T.; Pan, M.H. Se-Methyl-L-selenocysteine Induces Apoptosis via Endoplasmic Reticulum Stress and the Death Receptor Pathway in Human Colon Adenocarcinoma COLO 205 Cells. J. Agric. Food Chem. 2015, 63, 5008–5016.
  109. Ibanez-Redin, G.; Furuta, R.H.M.; Wilson, D.; Shimizu, F.M.; Materon, E.M.; Arantes, L.; Oliveira, O.N. Screen-printed interdigitated electrodes modified with nanostructured carbon nano-onion films for detecting the cancer biomarker CA19-9. Mater. Sci. Eng. C Mater. Biol. Appl. 2019, 99, 1502–1508.
  110. Negi, J.S.; Singh, P.; Joshi, G.P.; Rawat, M.S.; Bisht, V.K. Chemical constituents of Asparagus. Pharm. Rev. 2010, 4, 215–220.
  111. Saxena, V.K.; Chaurasia, S. A new isoflavone from the roots of Asparagus racemosus. Fitoterapia 2001, 72, 307–309.
  112. Hamdi, A.; Jaramillo-Carmona, S.; Srairi Beji, R.; Tej, R.; Zaoui, S.; Rodriguez-Arcos, R.; Guillen-Bejarano, R. The phytochemical and bioactivity profiles of wild Asparagus albus L. plant. Food Res. Int. 2017, 99, 720–729.
  113. Jaramillo-Carmona, S.; Guillen-Bejarano, R.; Jimenez-Araujo, A.; Rodriguez-Arcos, R.; Lopez, S. In Vitro Toxicity of Asparagus Saponins in Distinct Multidrug-Resistant Colon Cancer Cells. Chem. Biodivers. 2018, 15, e1800282.
  114. Zhang, W.; He, W.; Shi, X.; Li, X.; Wang, Y.; Hu, M.; Qin, Z. An Asparagus polysaccharide fraction inhibits MDSCs by inducing apoptosis through toll-like receptor 4. Phytother. Res. 2018, 32, 1297–1303.
  115. Wang, J.; Liu, Y.; Zhao, J.; Zhang, W.; Pang, X. Saponins extracted from by-product of Asparagus officinalis L. suppress tumour cell migration and invasion through targeting Rho GTPase signalling pathway. J. Sci. Food Agric. 2013, 93, 1492–1498.
  116. Bousserouel, S.; Le Grandois, J.; Gosse, F.; Werner, D.; Barth, S.W.; Marchioni, E.; Raul, F. Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model. Int. J. Oncol. 2013, 43, 394–404.
  117. Tse, G.; Eslick, G.D. Cruciferous vegetables and risk of colorectal neoplasms: A systematic review and meta-analysis. Nutr. Cancer 2014, 66, 128–139.
  118. Burow, M.; Bergner, A.; Gershenzon, J.; Wittstock, U. Glucosinolate hydrolysis in Lepidium sativum—Identification of the thiocyanate-forming protein. Plant Mol. Biol. 2007, 63, 49–61.
  119. Koroleva, O.A.; Davies, A.; Deeken, R.; Thorpe, M.R.; Tomos, A.D.; Hedrich, R. Identification of a New Glucosinolate-Rich Cell Type in Arabidopsis Flower Stalk. Plant Physiol. 2000, 124, 599–608.
  120. Clarke, J.D.; Dashwood, R.H.; Ho, E. Multi-targeted prevention of cancer by sulforaphane. Cancer Lett. 2008, 269, 291–304.
  121. Ramos-Gomez, M.; Kwak, M.K.; Dolan, P.M.; Itoh, K.; Yamamoto, M.; Talalay, P.; Kensler, T.W. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc. Natl. Acad. Sci. USA 2001, 98, 3410–3415.
  122. Gupta, P.; Kim, B.; Kim, S.H.; Srivastava, S.K. Molecular targets of isothiocyanates in cancer: Recent advances. Mol. Nutr. Food Res. 2014, 58, 1685–1707.
  123. Higgins, L.G.; Kelleher, M.O.; Eggleston, I.M.; Itoh, K.; Yamamoto, M.; Hayes, J.D. Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox–cycling agents. Toxicol. Appl. Pharmacol. 2009, 237, 267–280.
  124. Keum, Y.S.; Yu, S.; Chang, P.P.; Yuan, X.; Kim, J.H.; Xu, C.; Han, J.; Agarwal, A.; Kong, A.N. Mechanism of Action of Sulforaphane: Inhibition of p38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element-Mediated Heme Oxygenase-1 in Human Hepatoma HepG2 Cells. Cancer Res. 2006, 66, 8804–8813.
  125. Kim, J.K.; Gallaher, D.D.; Chen, C.; Gallaher, C.M.; Yao, D.; Trudo, S.P. Phenethyl isothiocyanate and indole-3-carbinol from cruciferous vegetables, but not furanocoumarins from apiaceous vegetables, reduced PhIP-induced DNA adducts in Wistar rats. Mol. Nutr. Food Res. 2016, 60, 1956–1966.
  126. Byun, S.; Shin, S.H.; Park, J.; Lim, S.; Lee, E.; Lee, C.; Sung, D.; Farrand, L.; Lee, S.R.; Kim, K.H.; et al. Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization. Mol. Nutr. Food Res. 2016, 60, 1068–1078.
  127. Choi, H.J.; Lim, D.Y.; Park, J.H. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,30-diindolylmethane in HT-29 human colon cancer cells. BMC Gastroenterol. 2009, 9, 39.
  128. Johnson, I.T. Cruciferous Vegetables and Risk of Cancers of the Gastrointestinal Tract. Mol. Nutr. Food Res. 2018, 62, e1701000.
  129. Shebaby, W.N.; Bodman-Smith, K.B.; Mansour, A.; Mroueh, M.; Taleb, R.I.; El-Sibai, M.; Daher, C.F. Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways. J. Med. Food. 2005, 18, 745–752.
  130. Purup, S.; Larsen, E.; Christensen, L.P. Differential effects of falcarinol and related aliphatic C-polyacetylenes on intestinal cell proliferation. J. Agric. Food Chem. 2009, 57, 8290–8296.
  131. Pan, M.H.; Ho, C.T. Chemopreventive effects of natural dietary compounds on cancer development. Chem. Soc. Rev. 2008, 37, 2558–2574.
  132. Sriamornsak, P. Chemistry of pectin and its pharmaceutical uses: A Review. Silpakorn Univ. Int. J. 2003, 3, 206–228.
  133. Ciriminna, R.; Fidalgo, A.; Delisi, R.; Tamburino, A.; Carnaroglio, D.; Cravotto, G.; Pagliaro, M. Controlling the Degree of Esterification of Citrus Pectin for Demanding Applications by Selection of the Source. ACS Omega 2017, 2, 7991–7995.
  134. Jalili-Nik, M.; Soltani, A.; Moussavi, S.; Ghayour-Mobarhan, M.; Ferns, G.A.; Hassanian, S.M.; Avan, A. Current status and future prospective of Curcumin as a potential therapeutic agent in the treatment of colorectal cancer. J. Cell. Physiol. 2018, 233, 6337–6345.
  135. Ismail, N.I.; Othman, I.; Abas, F.; Lajis., N.H.; Naidu, R. Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 2454.
  136. He, S.; Simpson, B.K.; Sun, H.; Ngadi, M.O.; Ma, Y.; Huang, T. Phaseolus vulgaris lectins: A systematic review of characteristics and health implications. Crit. Rev. Food Sci. Nutr. 2018, 58, 70–83.
  137. Hangen, L.; Bennink, M.R. Consumption of black beans and navy beans (Phaseolus vulgaris) reduced azoxymethane-induced colon cancer in rats. Nutr. Cancer 2002, 44, 60–65.
  138. Law, B.M.H.; Waye, M.M.Y.; So, W.K.W.; Chair, S.Y. Hypotheses on the Potential of Rice Bran Intake to Prevent Gastrointestinal Cancer through the Modulation of Oxidative Stress. Int. J. Mol. Sci. 2017, 18, 1352.
  139. Ryan, E.P.; Heuberger, A.L.; Weir, T.L.; Barnett, B.; Broeckling, C.D.; Prenni, J.E. Rice bran fermented with Saccharomyces boulardii generates novel metabolite profiles with bioactivity. J. Agric. Food Chem. 2011, 59, 1862–1870.
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