Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

Table 6

Quercetin 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
Flavonols	Quercetin	Fruits, vegetables, leaves, and grains	In vitro; HepG2 cells; 10, 20, and 40 M	Apoptotic cell death by regulating cell cycle and ↓ antiapoptotic proteins (Sp1 and Sp1 regulatory protein)	Lee et al. (2015) [27]
		Berries, grapes, potatoes, tomatoes, and onions; Beverages (tea, wine, and bear)	In vitro; HepG2 cell line; 12.5–100 M	↑ G2/M phase arrest accompanied by an ↑ apoptotic cell death apoptosis via ↑ p53, ↑ p21, ↓ Cyclin D1, ↓ Cdk2, Cdk7 levels, and ↑ ROS	Li et al. (2014) [28]
			In vitro; HepG2 cells; 50 M	↑ p16-mediated cell cycle arrest and ↑ apoptosis	Zhao et al. (2014) [105]
			In vivo; DEN induced liver cancer rats; 10 mg/kg	↑ apoptosis, ↑ caspase 9 ↑ caspase 3, and ↑ PARP; (the intrinsic mitochondrial pathway); ↓ lipid peroxidation; ↓ NFB	Vásquez-Garzón et al. (2013) [106]
			In vitro/in vivo; Hepatoma SMMC7721 cells and QGY7701 cells/athymic BALB/c nu/nu mice; 0–150 M/100 mg/kg	↑ DOX-mediated apoptosis in p53-dependent hepatoma cells; ↓ Bcl-xl	Wang et al. (2012) [83]
			In vitro; HepG2 cells; 50 mol/L	↓ HSPs in HepG2 cells	Zhou et al. (2011) [107]
			In vitro; HepG2; 50 M	↓ NF-B ↓ caspase-3, ↓ p38MAPK, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins, ↑ JNK, and ↑ AP-1 regulation of survival/proliferation (AKT, ERK)	Granado-Serrano et al. (2010) [108]
			In vitro; HA22T, VGH, and HepG2 cells; 40 M	↑ oxidative stress, ↑ ROS; ↑ apoptotic action of 2-methoxyestradiol	Chang et al. (2009) [109]
			In vitro; HepG2 and SK-Hep1; 20, 100, and 200 M	↑ TRAIL-induced apoptosis via ↑ Sp1-mediated DR5 and ↓ c-FLIPS	Kim et al. (2008) [110]
			In vitro; HepG2; 50 M	Tight regulation of survival/proliferation pathways via ↓; PI3/AKT, ↓ ERK, ↓ PKC-α, ↑ JNK, and ↑ PKC-delta	Granado-Serrano et al. (2008) [82]
			In vitro; HepG2 cells; 10–50 mol/L	↑ caspase-3, ↑ caspase -9, ↓ Bcl-xL/Bcl-xS,; ↓ major survival signals, ↓ Akt, and ↓ ERK	Granado-Serrano et al. (2006) [42]

For abbreviations see footer of Table 1.