Table 1.

Natural substances targeting DNA methylations associated with breast cancer

Phytochemicals/plant foods	Mechanism of intervention	Type of BC research	References
Curcumin	Decrease in promoter methylation status (RASSF1A, glutathione S-transferase P1) or DNA methylation activity	MCF-7 cells	[25, 27]
EGCG, genistein, withaferin A, curcumin, resveratrol, guggulsterone	Decrease in DNMT1, DNMT3a, and DNMT3b expressions	MCF-7 and MDA-MB 231 cells	[28]
Sulforaphane	Global DNA hypomethylation, decrease in DNMT1 and DNMT3 activity, and m6A RNA methylation	MCF-7 MDA-MB 231, and SK-BR-3 cells	[29]
Sulforaphane + EGCG	ERα promoter hypomethylation and hyperacetylation	MDA-MB 231 cells	[30]
Sulforaphane	PTEN and RARbeta2 promoter hypomethylation	MCF-7 and MDA-MB 231 cells	[31]
Resveratrol + pterostilbene	Decrease in DNMTs activity	HCC1806 and MDA-MB-157 breast cancer cells	[32]
Withaferin A	Epigenetic reprogramming through DNA hypermethylation	MDA-MB-231, MCF-7 cells	[33]
Green tea polyphenols +5-aza-2′-deoxycytidine	Decrease in HDAC1, DNMT1, DNMT3b, and MBD4 activity	MDA-MB-231, MCF-7 cells	[34]
Kazinol Q	Inhibition of DNMT1 activity	MDA-MB-231 cells	[36]
Genistein	Decrease in global DNA methylation, DNMT activity, and DNA methylation of several promoters (ATM, APC, PTEN, SERPINB5)	MCF-7 and MDA-MB-231 cells	[37]
Wild yam root extract	Activation of GATA3 gene in ER- cells	MCF-7 and MDA-MB-231 cells	[35]
Wild thyme	Inhibition of DNMT and HDAC activities	MDA-MB-231 cells	[38]
Isoliquiritigenin	Demethylation of WIF1 promoter, decrease in DNMT1 activity	Mouse BC model	[41]
Olive oil	Increase in global DNA methylation	Rat BC model	[39]
Corn oil	Increase in DNMT methylation and promoter methylation of RASSF1A and TIMP3	Rat BC model	[39]
Clove buds (mixture of phenolic acids, flavonol glucosides, tannins and phenolic volatile oils – eugenol, acetyl eugenol)	Increase in total RASSF1A promoter methylation	Rat BC model	[40]
Fruits/vegetables	Increase in global DNA methylation	Hispanic BC survivors	[42]
Vegetables	Increase in DNA methylation of LINE-1 after 6 and 12 months	Hispanic, African American, and Afro-Caribbean overweight and sedentary BC survivors	[43]
Folate + cobalamin	Hypomethylation of RARB and BRCA1 promoters	BC tissue samples of Iranian women	[44]
Riboflavin + pyridoxine	Hypermethylation of RARB promoter	BC tissue samples of Iranian women	[44]

EGCG, epigallocatechin gallate; DNMT, DNA methyltransferase; ER, estrogen receptor; HDAC, histone deacetylase; MBD, methyl-CpG-binding domain