Table 3.

Regulation of β-Catenin Signaling by Anti-Cancer Agents in HCC Treatment

Anti-Tumor Agent	In vitro/In vivo	Cell Line/Animal Model	Study Design	Remarks	Refs
Aplykurodin A	In vitro	Hep3B and SNU475 cells	20 and 40 μM	Apoptosis induction	[286]
				Decreasing proliferation rate of cancer cells
				Down-regulating β-catenin expression
Manuka honey	In vitro	HepG2 cells	1.25–20% w/v	Apoptosis inhibition	[287]
				Enhancing sensitivity of cancer cells to doxorubicin
				Suppressing Wnt/β-catenin signaling
Phyllanthus urinaria L	In vitro In vivo	HepG2, SMMC-7721, Huh-7 cells Xenotransplantation model	30, 60 and 120 μg/mL	Inducing proteasomal degradation of β-catenin via autophagy inhibition	[288]
				Impairing metastasis of cancer cells
Piplartine	In vitro	HepG2 and SMMC-7721 cells	0, 5, 10, 15 and 20 μM	Suppressing growth and metastasis of HCC cells	[289]
				Enhancing expression level of LINC01391 as tumor-suppressor factor
				Subsequent inhibition of Wnt/β-catenin axis
Canagliflozin	In vitro In vivo	Huh7 and Hep3B Huh7 xenograft tumor model	0–100 μM 300 mg/kg/day	Increasing β-catenin phosphorylation to mediate its proteasomal degradation	[290]
				Impairing tumor cell growth
				Enhancing survival rate of animal models
Evodiamine	In vitro In vivo	HepG2, SMMC-7721, and H22 cells Nude mice	20 mg/kg	Inhibiting β-catenin signaling	[291]
				Suppressing angiogenesis via down-regulating VEGFa expression level
				Acting as anti-cancer agent
Bruceine D	In vitro In vivo	Huh7 and Hep3B HCC cell lines HCC xenograft model	0.75 and 1.5 mg/kg	Triggering proteasomal degradation of β-catenin	[292]
				Inhibiting its nuclear translocation
				Down-regulation of Jagged 1
				Suppressing tumor growth
Paris saponin H	In vitro In vivo	Huh7 and PLC/PRF/5 cells Nude mice	0–20 μM 5 mg/kg	Exerting anti-tumor activity in a dose-dependent manner	[293]
				EMT inhibition
				Reducing β-catenin expression
				Inhibiting tumor growth in vitro and in vivo

Abbreviations: VEGF, vascular endothelial growth factor; EMT, epithelial-to-mesenchymal transition; HCC, hepatocellular carcinoma.