Table 2.

Natural substances inducing histone chemical modifications associated with breast cancer

Phytochemicals/plant foods	Mechanism of intervention	Type of BC research	References
EGCG	Alteration of histone acetylation and methylation status, ERα reactivation	MDA-MB-231 cells	[61]
EGCG	Inhibition of HATs activities, hTERT promoter hypomethylation and histone deacetylations (acetyl-H3, acetyl-H3K9, and acetyl-H4)	MCF-7, MDA-MB-231 cells	[62]
Curcumin and garcinol,	Reduction in H3K18ac (garcinol), elevated global levels of H4K16ac and H4K20m3 (garcinol), increased global levels of H3K18ac and H4K16ac (curcumin)	MCF-7 cells	[64]
3,4′-dimethoxy-3′,5,7-trihydroxyflavone from Myoporum bontioides L.	Downregulation of HDAC2 and HDAC4 expression, increase of H3ac	MCF-7 cells	[50]
Secoiridoids	Histone hyperacetylation	JIMT-1 cells	[65]
Diallyl disulphide/garlic oil	HDAC inhibition	MCF-7 cells	[66]
Luteolin (flavonoid)	HDAC inhibition	MCF-7/6 and MDA-MB231–1833 cells	[68]
Triterpenoid 5β,19-epoxy-19-methoxycucurbita-6,23-dien-3β,25-diol from Momordica charantia L.	Downregulation of HDAC1, increase in H3ac	MCF-7	[69]
Soy phytoestrogens (isoflavones)	Histones demethylation and acetylation (H3K27me3, H3K9me3, H3K4me3, H4K8ac, and H3K4ac)	MCF-7 and MDA-MB 231 cells	[75]
Genistein	Histones modification in theERα promoter, reactivation of ERα expression	Mouse BC model using MDA-MB-231 cells	[74]
Genistein	Histone modifications in the promoters of p21 and p16 genes	HMECs, SH, SHR, MDA-MB-231	[76]
Clove buds (mixture of phenolic acids, flavonol glucosides, tannins and phenolic volatile oils – eugenol, acetyl eugenol)	Increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac)	Rat BC model	[40]
Extra virgin olive oil	Decrease in H4K20m3 levels in mammary tumors or glands	Rat BC model	[39]

EGCG, epigallocatechin gallate; ER, estrogen receptor; HDAC, histone deacetylase; HAT, histone acetyltransferase