Table 2.

DNA methyltransferase (DNMT) inhibitors in HCC. The table shows the most prominent DNMT inhibitors, the changes in the targets of the inhibited DNMTs, and the resulting effects on the tumor.

DNMT inhibitor	DNMT targets affected	Effect	Ref.
5-Azacytidine	SLC10A1, CYP3A4, ALB, and miR-122	Inhibits tumor growth	[29]
Decaitabine	p16INK4A (activation)	G1 cell cycle arrest	[35]
	PRSS3 (activation)	Inhibits proliferation and migration	[36]
Guadecitabine (SGI-110)	DLEC1, RUNX3, and p16INK4A	Inhibits tumor growth	[38]
Zebularine	CDK2, Bcl-2, and phosphorylation of Rb (inhibition) and p21WAF/CIP1 and p53 (activation)	Inhibits proliferation and induces apoptosis	[42]
SGI-1027	Bcl-2 (inhibition) and BAX (activation)	Induces apoptosis	[222]
CM-272	E-cadherin, CYP7A1, FBP1, GNMT, and MAT1A (activation)	Inhibits proliferation and decreases adaptation to hypoxia	[223]
EGCG (Y6)	P-gp and HIF1-α (inhibition)	Inhibits proliferation and reverses doxorubicin-resistance	[53]
Genistein	CYP1A1, CYP1B1, and p-AMPK (activation) and CYP26A1 and CYP26B1 (inhibition)	Inhibits proliferation (at a 10-40 μM concentration) and induces apoptosis	[44]

ALB: albumin; BAX: Bcl-2-like protein 4; Bcl-2: B-cell lymphoma 2; CDK2: cyclin-dependent kinase 2; CYP1A1: cytochrome P450 1A1; CYP1B1: cytochrome P450 1B1; CYP26A1: cytochrome P450 26A1; CYP26B1: cytochrome P450 26B1; CYP3A4: cytochrome P450 3A4; CYP7A1: cholesterol 7α-hydroxylase-1; DLEC1: deleted in lung and esophageal cancer 1; FBP1: fructose-1,6-bisphosphatase; GNMT: glycine-N-methyl transferase; HIF1-α: hypoxia-inducible factor 1-α; MAT1A: methionine-adenosyltransferase 1A; p16INK4A: cyclin-dependent kinase inhibitor 2A; p21WAF/CIP1: cyclin-dependent kinase inhibitor 1; p53: tumor protein p53; p-AMPK: phosphorylated AMP-activated protein kinase; P-gp: P-glycoprotein 1; Rb: retinoblastoma; RUNX3: RUNX Family Transcription Factor 3; SLC10A1: sodium/bile acid cotransporter.