Epigenetics in hepatocellular carcinoma: An update and future therapy perspectives

Table 2 List of drugs targeting epigenetic modifications in hepatocellular carcinoma

Epigenetic modification	Targets	Drug(s)	Cell line/Animal model/Clinical trial phase	Results	Ref.
DNA methylation	DNA methyltransferase	Zebularine	Huh7 and KMCH cell linesHuman xenograft models	Zebularine-sensitive cell lines (Huh7 and KMCH) showed preferential demethylation of genes for tumor suppression, apoptosis, and cell cycle regulationIn vivo inhibition of tumor growth in xenograft model	[110]
	DNA methyltransferases	Zebularine	HepG2 cell line	Zebularine treatment inhibited cell proliferation and induced apoptosis in HepG2 cell line	[109]
	DNA methyltransferases	5-aza-2’-deoxycytidine	MMC-7721 and HepG2 cell lines	Inhibited telomerase activity, accompanied by reactivation of p16 and c-Myc. DAC synergized with cisplatin on growth inhibition	[111]
Histone acetylation	Histone deacetylase	Belinostat	PLC/PRF/5, Hep3B and HepG2 cell lines	Inhibited cell growth and induced apoptosis	[112]
	Histone deacetylase	Belinostat	Multi-center phase I/II clinical trial	Stabilized tumor in non-resectable advanced HCC	[115]
	Histone deacetylase	Suberoylanilide hydroxamic acid	HepG2, Hep3B and SK- Hep1 cell lines	Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis	[114]
Combination	Histone deacetylase + tyrosine kinase-inhibitors	Panobinostat + sorafinib	Huh7, Hep3B and HepG2 cell lines HCC xenograft model	Induction of apoptosisCombined panobinostat and sorafenib decreased vessel density, tumor volume and increased survival in HCC xenografts	[124]

HCC: Hepatocellular carcinoma.