Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

Table 2

Baicalein in HCC with possible mechanisms discussed in this paper.

Subfamily	Flavonoids	Typical origin	In vitro/in vivo; Cell lines/modes; Effective dose	Effects and related mechanisms	Author (year); References
Flavones	Baicalein	Scutellaria baicalensis (Scutellaria radix) roots (Sho-Saiko-To)	In vitro; HepG2 cells; 0, 12.5, 25 and 50 M	↑ protective autophagy, ↓ AKT/mTOR pathways; ↓ p-AKT, p-ULK1, and p-4EBP1	Wang et al. (2015) [20]
			In vitro; SMMC-7721 and Bel-7402; 100 M	↑ apoptosis via ER stress, possibly by ↓ Bcl-2 family, ↑ intracellular calcium, and ↑ JNK; ↑ protective autophagy	Wang et al. (2014) [93]
			In vitro/in vivo; H22, Bel-7404, and Hep G2/cancer inducible ICR mice; 0.5–100 g/mL/50 and 100 mg/kg	↑ G0/G1 cell cycle arrest, ↓ cancer cell proliferation, ↓ AKT ↓ β-catenin, and ↓ cyclin D1	Zheng et al. (2014) [21]
			In vitro/in vivo; MHCC97H cells/nude mouse model LCI-D20; 0, 10, 20, and 30 M/10 mg/kg/day	↓ tumor cell invasion, ↓ metastasis by ↓ cell motility; ↓ migration via ↓ ERK pathway, ↓ MMP-2, ↓ MMP-9, ↓ u-PA expression, ↑ TIMP-1, and ↑ TIMP-2 expression	Chen et al. (2013) [37]
			In vitro/in vivo; HepG2/HCC xenografts in mice; 40–120 M/N/A	↑ apoptosis, ↓ MEK1, ↓ ERK1/2, ↓ Bad, ↓ MTP, ↑ caspase-9, and ↑ caspase-3	Liang et al. (2012) [76]
			In vitro/in vivo; HA22T/VGH and SK-Hep1 cells/BALB c-nu mice; 10 M/5, 10, and 20 mg/kg/day	↓ adhesion, invasion, migration, and proliferation; ↓ metastasis; ↓ MMP-2, ↓ MMP-9, and ↓ uPA,; ↓ p50 and p65 nuclear translocation, and ↓ pIB-β; ↓ pPKCα and p38 MAPK	Chiu et al. (2011) [94]
			In vitro; Hep J5 cells; 10–100 M	↑ G2/M arrest and ↑ apoptosis (ER-dependent); ↑ cytochrome c release, ↑ caspase-9 and caspase-3, ↑ Bax/Bcl-2 ratio, ↑ AIF, and Endo G release from mitochondria	Kuo et al. (2009) [95]
			In vitro; Hep G2 cells; 25, 50, and 100 M	↑ G2/M population in Hep G2 cells; ↑ apoptosis and ↓ proliferation	Chang et al. (2002) [96]

For abbreviations see footer of Table 1.