Table 1.

Source, pharmacological effects and epigenetic mechanisms of action of promising natural compounds

Natural compound	Natural sources	Pharmacological effects	Epigenetic mechanisms of action
Folate, cobalamin, riboflavin, pyridoxine, methionine	Folate and riboflavin: spinach, asparagus, beans, peas, lentils, sunflower seeds, almonds	Anti-cancer, anti-proliferative, chemoprevention of malignant transformation	Regulation of one-carbon metabolism, SAM/SAH ratio, DNMT and MBD expression; regulation of miRNAs (tumour suppressor miR-122, miR-34a, miR-127, and oncogenic miR-21, miR-222)
	Cobalamin: fish, shellfish, poultry, milk, eggs
	Pyridoxine and methionine: grains, nuts, dragon fruit, sesame seeds
Retinoic acid	Vietnamese gac, crude palm oil, yellow and orange fruits (mango, papaya), orange root vegetables (carrots), spinach, sweet potatoes	Anti-cancer, anti-proliferative, differentiating, pro-apoptotic	Regulation of DNMTs expression and enzyme activity by affecting p21, AP-1, PTEN and ERs; regulation of miRNAs targeting DNMTs; regulation of tumour suppressor miRNAs (miR-15, miR-16, let-7a, let-7c, miR-34a, miR-342) and oncogenic miRNAs (miR-10a); GNMT regulation; histone acetylation
Vitamin D3	Sun exposure, fish, fish liver oils	Anti-cancer, anti-proliferative, differentiating, pro-apoptotic	Regulation of DNMTs expression and enzyme activity by affecting p21, AP-1, PTEN and ERs; regulation of histone acetylation; regulation of oncogenic miRNAs (miR-181a, miR-181b)
Resveratrol	Roots of hellebore, grapes, mulberries, apricots, pineapples, peanuts	Anti-cancer, antioxidant, anti-proliferative, anti-angiogenesis, anti-inflammatory, pro-apoptotic, cardioprotective	Regulation of DNMTs expression and enzyme activity by affecting p21, AP-1 and PTEN; activation of deacetylase SIRT1 and p300 HAT; down-regulation of UHRF1; regulation of miRNAs
Genistein and daidzein	Soybeans, lupin, kudzu, psoralea, fava beans, coffee	Anti-cancer, antioxidant, antihelminthic, anti-metastatic, cancer protective	Regulation of DNMTs expression and enzyme activity by affecting p21, AP-1 and PTEN; increase in HAT activity; regulation of miRNAs (tumour suppressor miR-1296, miR-16, and oncogenic miR-27a)
EGCG	Green tea	Anti-cancer, antioxidant, anti-proliferative, anti-angiogenesis, anti-inflammatory, pro-apoptotic, cancer protective	Regulation of SAM/SAH ratio by COMT-mediated reactions; direct inhibition of DNMTs by binding to catalytic domain of the enzyme; regulation of tumour suppressor miRNAs (miR-16)
Curcumin	Spice turmeric	Anti-cancer, antioxidant, protects against heart failure	Direct inhibition of DNMTs by binding to catalytic domain of the enzyme; inhibition of HDACs and p300 HAT; regulation of miRNAs (tumour suppressor miR-22, miR-15a, miR-16, and oncogenic miR-21, miR-199a)