Table 3.

Apoptotic effects of quercetin on liver cancer based on in vivo studies.

Type of Cancer	Animal Models	Mechanisms	Dosage	Duration	References
Hepatocellular	Chemically induced HCC rat model with injection of Diethylnitrosamine @200 mg/kg	↓ Liver enzymes—aminotransferase (ALT), ↓ aspartate aminotransferase (AST), ↓ alkaline phosphatase (ALP), ↓ total proteins (TP) and conjugated bilirubin (direct bilirubin), ↓ C-reactive protein (CRP), ↓ interleukin 6 (IL-6), ↓ lactate dehydrogenase (LDH), ↓ PIVKA-II and AFP, ↓ Ki-67 cells, ↓ TNFa, VEGF, p53 and NF-κB expression	Quercetin 50 mg/kg + sorafenib 7.5 mg/kg	13 weeks	[78]
Hepatoblastoma	BALB/c nude mice bearing HepG2 cells (1 × 107) cells	↓ Tumors grew slower and size, ↓ weighed, ↑ SIRT6, ↓ FZD4	10 mg/kg	28 days	[78]
Hepatocellular	BALB/c nude mice bearing SMMC7721 cells (2 × 106) cells	↑ Autophagosomes and autolysosomes, ↓ AKT/mTOR, ↑ MAPK, ↑cleaved caspase-3, ↑ BAX, ↓ Bcl-2, ↑ LC3A/B, ↓ p62, ↑ necrosis	60 mg/kg	10 days	[48]
Hepatocellular	Sprague Dawley rats (TAA Induced)	↓ Caspase-3, ↓↑ caspase-8, ↑ p53, ↓ cyclin D1 and Ki-67	TAA -200 mg/kg + Quercetin 100 mg/kg	21 days	[29]
Hepatocellular	Nude mice bearing LM3 cells	↓ Tumor volume, ↑ necrosis, ↑ TUNEL-positive cells, ↓ PCNA, ↑ Bax	100 mg/kg	21 days	[32]
Hepatocellular	BALB/c nu/nu nude mice bearing MHCC97H cells (1 × 107 cells)	↓ Tumor volumes, ↓ AP-2β and COX2 levels, ↑ TUNEL levels, ↓ cleaved caspase-9, ↓ cleaved caspase-3, ↓ cytoplasm Cyto-c, ↓ phosphorylated IKKα, IκBα and NF-κB	30, 40 and 50 mg/kg Quercetin nanoparticles	35 days	[49]
Hepatocellular	BALB/C nude mice bearing HuH-cells	↓ Tumor volume, ↑ survival rate	ZD55-TRAIL was injected intra-tumorally at 1 × 109 plaque-forming units + Quercetin 150 mg/kg	49 days	[79]
Hepatocellular	BALB/c nude mice	↑ 5-fluorouracil (5-FU) therapeutic efficacy, ↑ apoptosis, ↓ tumor growth	Quercetin 40 mg/kg and 5-fluorouracil 30 mg/kg	23 days	[28]
Liver	Wistar rats (two-phase model of hepato carcinogenesis)	↓ Number and volume of preneoplastic lesions, ↑ apoptosis, ↓ proliferative index, ↓ cell percentages ↓ M phase, ↓ cyclin D1, ↓ cyclin A, ↓ cyclin B, ↓ cyclin-dependent kinase 1, ↑ peroxisome proliferator, ↑ caspase-3 activity, ↑ Bax/Bcl-2, ↑ cytosolic cytochrome c	10 and 20 mg/kg	42 days	[27]
Hepatoma	C57BL/6N mice bearing LL/2 Lewis lung cancer (1 × 106)	↓ Tumor growth, ↓ tumor volume, ↓ HSP70, ↑ apoptosis rate	Liposomal Quercetin -50 mg/kg	15 days	[103]
Hepatoma	BALB/c mice bearing H22 tumor models (5 × 105)	↓ Tumor growth, ↓ tumor volume, ↓ HSP70, ↑ apoptosis rate	Liposomal Quercetin -50 mg/kg	15 days	[103]