Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer
Abstract
:1. Introduction
2. Epigenetic Mechanisms
2.1. DNA Methylation
2.2. Histone Modifications
2.3. Non-Coding RNAs
3. Phytochemicals Targeting Enzymes Involved in Epigenetic Regulation
3.1. Flavan-3-ols
Compounds FLAVAN-3-OLS | Epigenetic Effects | High Content Food Quantity mg/100 g [81] | Role in Pathological Conditions |
---|---|---|---|
(−)-Epigallocatechin 3-gallate (EGCG) SubClass: Flavan-3-ols Class: Flavonoids Family: Polyphenols | Inhibition of DNMT activity (mainly DNMT1) in breast, colon, prostate, and esophageal cancer cells [61] Inhibition of hTERT promoter methylation in breast, lung, oral cavity, liver, and thyroid tumor cells [61] Demethylation of SCUBE2 promoter, inhibiting the epithelial-mesenchymal transition [80] Modulation of HAT activity [60] Regulation of miRNA expression in hepatocellular carcinoma and gastric cancer in vivo, targeting c-Kit, Bcl2, E2F, and RAS [62] | Carob Flour (109.40), Green tea (70.20), White tea (42.45), Oolong tea (34.48), Black tea (9.36), Nuts pecans (2.30), Fuji Apple with skin (1.93), Hazelnut (1.06), Cranberry (0.97), Blackberry (0.68), Raspberry (0.54), Plum (0.48), Pistachio nuts (0.40), Peach (Prunus persica) (0.30), Granny Smith Apple, with skin (0.24), Golden Delicious Apple, with skin (0.19), Pear (0.19), Avocado (0.15), Red Delicious Apple, with skin (0.13), Gala Apple, with skin (0.11), Strawberry (0.11) | Reduction in oxidative stress, angiogenesis, and inflammation in tumors [82] Cancer prevention [83,84] Induction of apoptosis by activating caspase 9, 8, and 3 and upregulating Bax protein in cancer cells [85] Induction of cell cycle arrest by enhancing p21 and p27 expression in tumor cells [85] |
(−)-Epicatechin (EC), Epicatechin-3-gallate (ECG) Epigallocatechin (EGC) SubClass: Flavan-3-ols Class: Flavonoids Family: Polyphenols | Inhibition of DNMT activity [64] Regulation of HAT activity [20] Modulation of miRNA expression in cancer [63] | (−)-Epicatechin: Cocoa powder (158.3) Baking chocolate (141.83), Cacao seed (99.18), Grape seed (93.31), Dark chocolate (84.80), Soybean, mature seed (37.41), Broad beans, immature seed (Vicia faba) (28.96), Apple, skin only (28.73), Blueberry (25.66), Green tea, Quingmao (20.80), Sour cherry juice (12.97), Milk chocolate (10.88), Alcoholic beverage, red wine (10.66–3.79), Apple (9.83–4.09), Grape, black (Vitis vinifera) (8.68), Cherry (Prunus avium) (5.00), Apricot (Prunus armeniaca) (4.74), Apple juice (4.70), Blackberry (4.66), Cranberry (4.37), Peache, white, (4.09), Pear, raw (Pyrus communis) (3.76), Raspberry (Rubus spp.) (3.52), Plum (3.20), Nectarine (Prunus persica) (3.06–2.34), Buckwheat flour, whole-groat (3.02), Cranberry bush berries (Viburnum opulus) (2.69), Oolong tea (2.54), Vinegar, wine, red (2.20), Black tea (2.13), Arctic bramble berries (1.80), Grape, white (1.70), Strawberry tree fruit (Arbutus unedo) (1.56), Pistachio nuts (Pistacia vera) (0.83), Nut pecans (Carya illinoinensis) (0.82), Vinegar, cider (0.82), Cloudberry (0.80), Kiwifruit, gold (Actinidia chinensis) (0.64), Nut almonds (Prunus dulcis) (0.60), Alcoholic beverage, white wine (0.55), Medlar (Mespilus germanica) (0.53), Rhubarb (Rheum rhabarbarum) (0.51), Fig (Ficus carica) (0.50), Currants, European black (Ribes nigrum) (0.47) Epicatechin-3-gallate and Epigallocatechin: Cocoa powder (196.43), Cacao Bean (99.18), Carob Flour (30.06), Green tea (8.33), White tea (8.35), Oolong tea (2.54), Black tea (2.11), Nut almond (0.60), Nut pecan (0.82) | Antioxidative, anti-inflammatory, and anticancer effects [20] |
(+)-Catechin, (+)-Gallocatechin SubClass: Flavan-3-ols Class: Flavonoids Family: Polyphenols | Inhibition of DNMT activity [64] Regulation of HAT activity [20] Modulation of miRNA expression in cancer [63] | (+)-Catechin: Blueberry (98.47), Cacao Bean (88.45), Grape seed (74.63), Tea green, Quingmao (67.60), Cacao powder (64.82), Carob Fluor (50.75), Blackberry (37.06), Cranberry (29.04), Chocolate, dark (24.20), Cocoa powder (21.51), Plum Black Diamond(17.22), Broad bean (Vicia faba) (14.29), Peache white (12.25), Grape Black (10.14), Nectarine (Prunus persica) (7.58), Apple skin only (7.40), Nut Pecan (7.24), Alcoholic beverage, wine red (from 6.21 to 7.70) Strawberry (6.70), Chard, red leaf (Beta vulgaris) (6.70), Apple (6.67–0.75) Banana (6.10), Blueberry (5.29), Bean, pinto (Phaseolus vulgaris) (5.07). Cider (4.85), Green tea (4.47), Cherry (4.36), Milk chocolate (4.16), Grape, white (3.73), Apricot (3.67), Vinegar, wine (3.60), Pistachio nuts, (3.57), Jujube (Ziziphus jujuba) (3.21), Strawberry (3.11), Juice sour cherry (3.18), Plum (2.89), Barley, hulled (Hordeum vulgare L.) (2.39), Arctic bramble berry (2.30), Rhubarb (Rheum rhabarbarum) (2.17), Mango (1.72), Gooseberry (1.67), Raspberry (1.31), Currants, red (1.27), Apple juice (1.25), Black tea (1.51), Nut, hazelnut or peanut (Corylus spp.) (1.19), Quinces (0.75) (+)-Gallocatechin: Cacao Bean (8262.00), Broad bean, immature seeds (Vicia faba) (4.15), Strawberry tree fruit (Arbutus) (1.60), Green Tea (1.54), Currants, red (1.28), Black tea (1.25), Pomegranate, raw (0.17), Persimmon (0.17), Star apple (0.53) | Antioxidative, anti-inflammatory, and anticancer effects [20] |
Thearubigins SubClass: Flavan-3-ols Class: Flavonoids Family: Polyphenols | Inhibition of DNMT activity [86] | Black tea (81.30) | Antioxidative, anti-inflammatory, and anticancer effects [87,88] |
3.2. Flavonols
Compounds FLAVONOLS | Epigenetic Effects | High Content Food Quantity mg/100 g | Role in PATHOLOGICAL Conditions |
---|---|---|---|
Kaempferol SubClass: Flavonols Class: Flavonoids Family: Polyphenols | Inhibitory activity towards HDAC enzymes in human hepatoma and colon cancer cell lines [65] Promotion of H3 histone hyperacetylation in hepatoma and colon tumor cells [65] Binding to DNMT1 in colorectal cancer cell lines, thus downregulating DACT2 methylation and inhibiting Wnt/β-catenin pathway [90] Regulation of miR-340 expression in lung tumor [7,66] | Caper (259.19), Caper canned (131.34), Kale (46.80), Arugula (34.89), Mustard green (38.30), Ginger (33.60), Watercress (23.03), Radish (21.85), Chia seed (12.30), Chives (10.0), Chard (9.20), Collards (8.74), Broccoli (7.84), Lovage (Levisticum officinale) (7.0), Fennel leaves (6.50), Dried Goji berries (6.20), Cherry powder (5.14), Thistle (3.80), Chicory green (2.45), Corn poppy (Papaver rhoeas) (2.30), Blueberry (1.66), Black Tea (1.41), Asparagus (1.39), Bee Pollen granules (1.12), Acerola (1.05), Green Tea (1.00), Ribes Nigrum (0.71), Red onion (0.70), Elderberry (0.51), Strawberry (0.49), Carob Flour (0.44), Grapefruit (0.40), Lingonberry (0.38), Blackberry (0.27), Apple (0.14), Cranberry (0.12) | Inhibition of fat formation, nervous system protection, and heart protection [87] Antioxidant, antiallergic and anticancer effects [87] Promotion of autophagic cell death in gastric tumor cells; inhibition of cancer cell proliferation and induction of cell apoptosis in lung tumor [7,66] |
Quercetin SubClass: Flavonols Class: Flavonoids Family: Polyphenols Current dosage: 500 mg quercetin/day, 12 weeks Mean intake by fruits or vegetables: 5–500 mg/day IC50: 1.6 µmol/L | Reduction in the activity of DNMTs, HMTs, and HDACs, and activation of HATs in cervical tumor cells [66] Regulation of different miRNAs (like miR-145 and miR-146) and regulatory axes (such as miR-22/WNT1/β-catenin and p53/miR-34a/SIRT1) in several tumor cell lines [7] | Caper (233.84), Caper canned (172.55), Levisticum (170.0), Juice concentrate Elderberry (108.16), Radish (70.37), Arugula (66.19), Corianders leaves (52.90), Peppers yellow wax (50.63), Fennel leaves (48.80), Juniper berries ripe (46.16), Red onion ((39.21), Watercress (29.99), Elderberries (26.77), Corn poppy (Papaver rhoeas) (26.30), Carob flour (38.78), Onion cooked boiled drained (24.36), Kale (22.58), Been pollen (20.95), Apple skin (19.36), Chia seed (18.20), Cherries powder (17.44), Thistle (16.50), Arugula (15.16), Asparagu cook boiled-drained (15.16), Cranberries (14.84), Asparagus (13.98), Goji berry dried (13.60), Lingonberries (13.30), Plums black Diamond (12.45), Lovage Mustard green (8.80), Blueberries (7.67), Chard (7.50), Chicory green (6.49), Chives (4.77), Acerola (4.74), Ribes Nigrum (4.45), Apple (4.01), Blackberries (3.58), Broccoli (3.26), Collards (2.57) | Antioxidant, anticancer, anti-inflammatory, antiviral, antibacterial, neuroprotective and hypolipidemic impact [66] Inhibition of cell proliferation by promoting let-7c, Numb1, and Notch, and induction of cell apoptosis in pancreatic tumor cells [91] Regulation of β-catenin signal and promotion of BRCA1 expression in triple-negative breast cancer [92] |
Fisetin SubClass: Flavonols Class: Flavonoids Family: Polyphenols IC50: 3.5 µmol/L | Inhibition of DNMT activity [95] Activation of SIRTs [97] | Strawberry (16.0), Apple (2.69), Persimmons (1.05), Onion (0.48), Grapes (0.39), Kiwi (0.2) | Interference with cancer cell growth, cell cycle progression, and promotion of cell apoptosis [95] Regulation of the Bcl-2 family protein expression and inhibition of signaling pathways in which p38 MAPK, ERK 1/2, or NF-kB are involved [96] |
Myricetin SubClass: Flavonols Class: Flavonoids Family: Polyphenols IC50: 1.2 µmol/L | Inhibition of DNMT activity in a concentration-dependent manner [20] Indirect modulation of deacetylation to induce HIF-1α expression and suppress cMyc and β-catenin expression [98] | Juice concentrate black currant (20.85), Fennel leaves (19.80), Goji berry dried (11.40), Arugula (7.92), Carob flour (6.73), Cranberries (6.63), Thistle (3.60), Ribes Nigrum (6.18), Been pollen (3.34), Swiss Chard (2.20), Red onion (2.16), Blueberries (1.30), Corn poppy (Papaver rhoeas) (1.10), Tea green (1.00), Blackberry (0.67), Black tea (0.45), Strawberry (0.35), Broccoli (0.06), Apple (0.01), Plums Black Diamond (0.01) | Prevention of cardiovascular disorders, anticancer ability, and reduction in blood lipid levels, blood pressure, and both diabetes and bacteriostasis complications [4] |
3.3. Flavones and Flavanones
Compounds FLAVONES and FLAVANONES | Epigenetic Effects | High Content Food Quantity mg/100 g | Role in Pathological Conditions |
---|---|---|---|
Apigenin SubClass: Flavones Class: Flavonoids Family: Polyphenols Dosage: 500–1000 mg | Inhibition of class I HDAC activity in prostate tumor cells [20,68] Acetylation of H3 histone in breast tumor cells [101] Inhibition of the activity of 5-cytosine DNMTs and silencing of NRF2 in skin epidermal cells [67] Induction of the expression of miR-16 and miR215-5p in glioma and colon cancer [7] | Parsley dried (4503.50), Celery seed (78.65), Vine Spinach (62.20), Kumquat (Citrus japonica) (21.87), Celery heart green (19.1), Red onion (0.24) | Inhibition of cell growth and promotion of cell cycle arrest and apoptosis in human prostate cancer cells [108] Blocking of the proliferation and growth of breast tumor cells through p21 transcription [101] Antioxidant and anticancer effects [67] |
Luteolin SubClass: Flavones Class: Flavonoids Family: Polyphenols | Inhibition of DNMT1 and HDAC enzymes in a dose-dependent manner in colorectal tumor cells [69] Modification of the acetylation pattern of the gene promoter histone in prostate cancer cells [103] Regulation of the expression of different miRNAs in several tumor cell lines [4] | Juniper berries ripe (Juniperus communis L.) (69.05), Parsley dried (19.75), Red onion (0.16) | Use against diabetes and Alzheimer’s disorder [4] Inhibition of proliferation and metastasis in breast tumors by regulating MMP9 expression and reversal of the epithelial-to-mesenchymal transition through the regulation of β-catenin expression [102] Promotion of apoptosis in colorectal tumor cells [69] |
Hesperetin SubClass: Flavanones Class: Flavonoids Family: Polyphenols | Reduction in methylation of the histone H3K79 in gastric cancer cells [105] Inhibition of DNMT activity [70] | Grapefruit (1.50), Citrus paradise (1.50) | Anticancer effects by reducing metastasis recurrence [20] |
Naringenin SubClass: Flavanones Class: Flavonoids Family: Polyphenols Dose: 500–1000 mg/day | Inhibition of DNMT and HDAC activity [70] Reduction in the expression of several miRNAs involved in anti-inflammatory and antioxidant mechanisms (including miR-17-3p and miR-25-5p) in human colon adenocarcinoma to upregulate GPX and SOD expression [107]) | Grapefruit (53.0), Citrus paradise (53.0) | Antidiabetic, liver and heart-protective, antiviral, antioxidant, and antitumor effects; use in sepsis treatment [106] Promotion of apoptosis in neuroblastoma cancer cells [70] |
3.4. Isoflavones and Anthocyanidins
Compounds ISOFLAVONES and ANTHOCYANIDINS | Epigenetic Effects | High Content Food Quantity mg/100 g | Role in Pathological Conditions |
---|---|---|---|
Genistein SubClass: Isoflavones Class: Flavonoids Family: Polyphenols (phytoestrogen group) | Activation of HAT activity and histone demethylation [73,74] Inhibition of DNMT enzymes [72] Modulation of several miRNAs in cancer [119] | Soy flour (89.42), Instant beverage Soy powder (62.18), Soy protein drink (42.91), Soy milk (42.85), Soybean (39.57), Natto (37.66), Tempeh (36.15), Miso (23.24), Green soybeans (22.57), Soy fiber (21.68) Soybean mature seeds (18.77), Tofu (16.01) Soy Yogurt (16.59) | Antitumor and antiproliferative effects [114] Suppressor of oncogene antiestrogenic activity [121] Induction of ROS-mediated apoptosis and reduction in epithelial-mesenchymal transition in both head and neck tumors, thus inhibiting tumor growth and proliferation [119] |
Daidzein SubClass: Isoflavones Class: Flavonoids Family: Polyphenol (phytoestrogen group) | Activation of HAT activity [122] Inhibition of DNMT enzymes [115] | Soy flour (67.69), Soy Milk, dried (40.85), Instant beverage soy powder (40.07), Natto (33.22), Soy protein drink (27.98), Tempeh (22.66), Soybeans (21.75), Green soybeans (20.34), Soy fiber (18.80), Miso (16.43), Tofu (15.59), Soy Yogurt (13.77), Soybean mature seeds (12.86) | Antiestrogenic activity [123] |
Delphinidin Subclass: Anthocyanidins Class: Flavonoids Family: Polyphenols | Inhibition of DNMT enzymes, which causes the activation of the Nrf2-ARE pathway [76] Increase in HDAC (in particular class I HDACs) activity [75] | Bilberry (97.59), Black currants (89.62), Eggplant (85.69), Blueberries (35.43), Black beans (18.50), Jambul (17.73), Red currants (9.32), Cranberries (7.67), Bananas (7.39), Pecans nuts (7.28), Jostaberry (6.61), Red onion (4.28), Red grapes (2.27) | Anticancer, antioxidative, and vision-protective functions; use in the prevention and treatment of type-2 diabetes and obesity [120] Upregulation of different pro-apoptotic genes and downregulation of anti-apoptotic ones [75] |
3.5. Other Compounds
OTHER PHYTOCHEMICALS | Epigenetic Effects | High Content Food | Role in Pathological Conditions |
---|---|---|---|
Curcumin Dosage: Curcuma longa powered 500 mg/day. Dosage Indian cook: 1–2 g/day | Regulation of both HAT and HDAC activities [126] Inhibition of DNMT activity [154] Inhibition of oncogenic miRNAs and promotion of tumor suppressor miRNAs [127] | Curcuma longa powder contains 2% curcumin; 1 g Curcuma contains 20 mg curcumin; 1 g Curry contains 2.9 mg curcumin | Modulation of intracellular pathways implicated in inflammation, proliferation, invasion, survival, and apoptosis in cancer [125] Cancer prevention and suppressor [127,129] Toxic effects at high doses in normal cells like human dermal fibroblasts, resulting in a pronounced arrest of cell cycle progression and higher levels of cell death [155] |
Folic Acid Family: Folate The recommended daily intake of folate for adults is about 400 µg. | A key element in the methyl-metabolism pathway [156] Regulation of the hepatic DNA methylation status [157] | Breakfast cereals Fortified (100–400 µg per 100 g), Peanuts (240 µg per 100 g), Black-eyed Peas (210 µg per 100 g), Fortified pasta (100–200 µg per 100 g), Spinach (194 µg per 100 g), Lentils (181 µg per 100 g), Chickpeas (Cicer arietinum) (172 µg per 100 g), Asparagus (149 µg per 100 g) Brussels Sprouts (140 µg per 100 g), Beetroot (Beta vulgaris subsp. vulgaris) (109 µg per 100 g), Lettuce (136 µg per 100 g), Broccoli (108 µg per 100 g), Almonds (50 µg per 100 g), Grains (20–40 µg per 100 g), Oranges (30 µg per 100 g), Eggs (22–47 µg per 100 g.), Bananas (20 µg per 100 g), Pasta (not fortified) (10–20 µg per 100 g) | Deficiency can modify hepatic DNA methylation patterns and induce liver (but also breast, lung, brain, and colorectal) cancer [158]. Antioxidant and pro-oxidant effects [159] |
Indole-3-carbinol (I3C) and diindolylmethane (DIM) | Proteasomal degradation of class I HDAC enzymes [133] Modulation of the expression of several miRNAs in cancer [160] | Cruciferae family (Brassicaceae) as Broccoli (15–25 mg/100 g), Cabbage (10–15 mg/100 g), Cauliflower (20–40 mg/100 g), Brussels Sprouts (40–50 mg/100 g), Mustard (10–15 mg/100 g), radish (all of Brassica genus) (1–4 mg/100 g) | Attenuation of symptoms of cigarette smoke [161] Anticancer effects, including promotion of apoptotic mechanisms in several tumor cell lines [132] |
Phenethyl isothiocyanate (PEITC) Family: Isothiocyanates | Inhibition of HDAC and DNMT activity [136] Induction of targeted histone acetylation and methylation in human prostate tumor cells [135] Regulation of the expression of several miRNAs in cancer [137] | Cruciferae family as Watercress, Cauliflower, Cabbage, Cress, Bok Choy (Brassica rapa subsp. Chinensis) (Chinese cabbage) (10–150 mg per 100 g); Radishes (Raphanus sativus) (1–4 mg per 100 g); Arugula (1–2 mg per 100 g). | Inhibition of carcinogenic processes and regulation of stress response and inflammation [134] |
Lycopene Family: Tetraterpenoid | Inhibition of DNMTs [139] | Tomato (2.5–4.5 mg per 100 g) Watermelon (4–7 mg per 100 g) Pink Grapefruit (1–3 mg per 100 g), Pink Guava (5–6 mg per 100 g), Papaya (2–3 mg per 100 g) | Antioxidant capacity, DNA protection from oxidative damage, reduction in tumor growth and proliferation in breast, prostate, liver and lung cancer [138] Protective agent against ultraviolet-related tumorigenesis [140] |
Resveratrol Family: Polyphenols | Promotion of HDAC activity [162] Resveratrol targets: SIRT1, -2 and -3 [162] H3 acetylation in breast cancer, enhancing the expression of BRCA1 [144] FOXO deacetylation in prostate cancer [163] Reduction in the expression of different oncogenic miRNAs in colon cancer cells [144] | Red grape skin (0.5–1.5 mg per 100 g), Red wine (0.2–5.8 mg per 100 mL), Blueberry, Mulberry, Cranberry (0.02–0.06 mg per 100 g), and Peanut (0.1–0.3 mg per 100 g) | Anti-inflammatory, anti-aging, and anticancer properties, which influence tumor cell proliferation, growth, invasion, and apoptosis [141] Promotion of apoptotic mechanisms in colon, breast, prostate tumor cells and leukemia [124] Anti-aging potential and suppression of mouse skin cancer in combination with tea polyphenols [162,164] |
Sulforaphane Family: Isothiocyanate | Inhibition of HDAC activity, regulation of histone methylation, and reduction in H1 histone phosphorylation [146] Inhibition of the activity of DNMTs, mainly DNMT1, -3a, and -3b, in cervical, prostate, and breast tumor cell lines [149,150] Regulation of the expression of several miRNAs in different human tumors [137,147] | Broccoli Sprouts (around 30–100 mg per 100 g), Cruciferae as Cabbage, Brussels Sprouts, Broccoli, Kale (Brassica oleracea var. Sabellica) (0.1–2.5 mg per 100 g) | Reduction in oxidative stress levels, inhibition of cell proliferation, and induction of cell apoptosis in cervical, pancreatic, liver, lung, and ovarian cancers [145] Promotion of the expression of several cytoprotective genes (such as catalase, glutathione S-transferase, and superoxide dismutase) through the epigenetic reactivation of the Nrf2 pathway [147] Cell protection from ultraviolet-associated tumorigenesis [165] |
4. Bioavailability of Bioactive Molecules
5. Phytochemicals and Traditional Anticancer Therapies: A Comparative Analysis Including Clinical Studies
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Casari, G.; Romaldi, B.; Scirè, A.; Minnelli, C.; Marzioni, D.; Ferretti, G.; Armeni, T. Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer. Biomolecules 2025, 15, 15. https://doi.org/10.3390/biom15010015
Casari G, Romaldi B, Scirè A, Minnelli C, Marzioni D, Ferretti G, Armeni T. Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer. Biomolecules. 2025; 15(1):15. https://doi.org/10.3390/biom15010015
Chicago/Turabian StyleCasari, Giulia, Brenda Romaldi, Andrea Scirè, Cristina Minnelli, Daniela Marzioni, Gianna Ferretti, and Tatiana Armeni. 2025. "Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer" Biomolecules 15, no. 1: 15. https://doi.org/10.3390/biom15010015
APA StyleCasari, G., Romaldi, B., Scirè, A., Minnelli, C., Marzioni, D., Ferretti, G., & Armeni, T. (2025). Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer. Biomolecules, 15(1), 15. https://doi.org/10.3390/biom15010015