Table 1.

Epigenetic targets of thymoquinone in cancer.

Epi-Target	Role of Epi-Target	Experimental Model	Mechanisms of Action	References
UHRF1	Reader	Human cervical carcinoma HeLa cells. T-ALL	TQ targeted the E3 ubiquitin ligase activity of UHRF1 resulting in an auto-ubiquitination of UHRF1 likely through the downregulation of HAUSP	[23]
		T-ALL	TQ upregulated p73 expression and cleaved caspase 3 leading to UHRF1 degradation	[63]
		T-ALL	TQ decreased the expression of PDE1A leading to the upregulation of p73 and downregulation of UHRF1	[62]
		T-ALL Human breast cancer cells	TQ decreased the expression of mRNA UHRF1 in dose-dependent mechanism	[60]
DNMT1 DNMT3A DNMT3B	Writer	Human acute myeloid leukemia cells Patient primary cells	TQ inhibited DNMT1 activity and decreased its expression through the disruption of Sp1/NFkB complex from DNMT1 promoter. TQ decreased the expression of DNMT3A through the upregulation of miR-29b, known to directly bind to the 3′-UTR of DNMT3A	[64]
		T-ALL	TQ decreased the expression of DNMT1 protein	[63]
		T-ALL	TQ decreased the expression of DNMT1, 3A,3B	[60]
HDAC1 HDAC2 HDAC3 HDAC4 HDAC9	Eraser	T-ALL	TQ decreased the expression of HDAC1 protein	[63]
		T-ALL	TQ decreased in the expression of HDAC1, 4 and 9	[60]
		T-ALL Human breast cancer cells	TQ decreased the expression of mRNA HDAC1 in dose-dependent mechanism	[60]
		Human pancreatic ductal adenocarcinoma cells. Human pancreatic ductal adenocarcinoma xenografts.	TQ inhibited HDAC activity, decreased the expression of HDAC 1, 2, 3 at mRNA levels and increased the acetylation of histone 4 at lysine 12 (H4 Ac-K12)	[65]
G9A	Writer	T-ALL Human breast cancer cells	TQ decreased the expression of mRNA G9A in dose-dependent mechanism	[60]