Table 6.

Studies of NCTD on promoting demethylation, modulating immune response and some other anticancer activities

Anticancer activities	Cancers	Cell lines	Basic mechanisms	Pathways	Accompanying roles	Experiment	Referencess
Promoting demethylation	NSCLC		Inhibiting proliferation, invasion, migration; inducing apoptosis and cell-cycle arrest; blocking β-beta-catenin; altering Bax, caspase-3, Bcl-2; activating WIF-1 and SFRP1; promoting WIF-1 demethylation, thus inhibits Wnt signal pathway	Promoting demethylation of WIF-1	Activating WIF-1 and SFRP1	In vitro	[125]
	Glioma	LN229 U251	Inhibiting proliferation, migration, invasion; inducing apoptosis and G2 phase cell-cycle arrest; downregulating Bcl-2, activating caspase-3; promoting WIF-1 and its demethylation; suppressing Wnt/β-catenin signaling, cyclin B1, and β-catenin/TCF-4; Bcl-2 and cleaved caspase-3	Inhibiting Wnt/β-catenin pathway via promoting WIF-1 demethylation	Activating WIF-1 and SFRP1	In vitro	[126]
	Hepatocellular cancer	HepG2	Inhibiting proliferation and RASSF1A methylation in a dose-dependent manner	Inhibiting RASSF1A methylation		In vitro	[121]
Modulating immune responses		Macrophages	Promoting the phosphorylation of AKT/p65 and transcriptional activity of NF-κB	Upregulation of AKT/NF-κB signaling pathway		In vitro In vivo	[127]
		Peripheral blood mononuclear cell (PBMC)	Blocking PHA-induced cyclins D3, E, A and B and IL-2 mRNAs expression; improving production of cyclin D3, E, A and B and IL-2; Cell cycle G0/G1 arrest; blocking cell proliferation			In vitro	[128]
Suppressing tumor glucose oxidative metabolism		Morris Hepatoma 7777	Suppressing tumour 14C-labelled glucose oxidative metabolism in rat Morris hepatoma			In vitro In vivo	[130]
Inhibiting NAT activity	Hepatocellular cancer	HepG2	NAT activity on acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid (PABA) were examined, inhibiting NAT activity			In vitro	[131]
The effect on leukemic stem cells	Acute myeloid leukemia	MV4-11	Decreasing HLF, inducing apoptosis by modulating HLF, SLUG, NFIL3 and c-myc, thereby inducing p53 and the mitochondrial caspase cascade, producing no myelosuppression			In vitro In vivo	[4]
Modulating macrophage polarization	Hepatocellular cancer	HepG2, mouse hepatoma H22, BMDM Raw 264.7	Inhibiting tumor growth, survival and invasion, decreasing a shift from M2 to M1 polarization and CD4+/CD25+ Foxp3 T cells in HCC microenvironment; inhibiting STAT3; enhancing M1 polarization through increasing miR-214 expression; inhibited β-catenin	Through miR-214 modulating macrophage polarization		In vitro In vivo	[23]