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Table 6 Studies of NCTD on promoting demethylation, modulating immune response and some other anticancer activities

From: Insight into norcantharidin, a small-molecule synthetic compound with potential multi-target 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]