Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

Table 4

Genistein 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
Isoflavones	Genistein	Dyer’s broom (Genista tinctoria)	In vitro; HepG2 cells; 1.0 and 10 M	Regulation of MDR proteins, ↑ P-gp, and ↑ MRP2 protein; nutrient-drug interactions, ↑ chemoresistance to sorafenib	Rigalli et al. (2015) [31]
			In vitro/in vivo; HepG2 cells/nude mice; 3, 6, and 9 M/50 mg/kg BW	↑ E-cadherin, ↑ -catenin, ↓ N-cadherin, and Vimentin; ↓ intrahepatic metastasis by ↓ EMT, which was correlated with ↓ NFAT1	Dai et al. (2015) [22]
			In vitro; HepG2, Huh-7, and HA22T3; dose dependent 20 μM	↓ NF-B, ↓ AP-1 ↓ MAPK, IB, and ↓ PI3K/Akt, ↓ MMP-9, and ↓ EGFR	Wang et al. (2014) [98]
			In vitro/in vivo; HCCLM3 cells/nude mice bearing human HCC xenografts; 40 mol/L/2 mg/kg/day for 4 weeks	Synergistic effect with geneistin via ↓ cisplatin-induced MMP-2 expression	Chen et al. (2013) [37]
			In vitro/in vivo; HepG2 and Hep3B/nude mice; 15 M and 20 M/50 mg/kg	↑ ATO suppressive effect via ↓ NF-B pathway, ↓ cyclin D1, ↓ Bcl-xL, ↓ Bcl-2, ↓ c-myc, ↓ COX-2, and ↓ VEGF	Ma et al. (2011) [99]
			In vitro; SK-Hep-1 cells; 0–50 M	↑ apoptosis ↑ Fas, ↑ FasL, and ↑ p53; ↑ Bcl-2, ↑ caspase-9 and ↑ caspase-3, and ↑ PARP cleavage	Fang et al. (2010) [100]
			In vitro/in vivo; HepG2, SK-Hep-1, and Hep3B/HepG2 xenografts in BALB/c nude mice; 15 M, 15 M, and 20 M/50 mg/kg	Synergistic effect with ATO via ↓ Bcl-2 expression, ↑ Bax expression, ↑ caspase-9 and -3, ↑ cytochrome c, and ↑ ROS	Jiang et al. (2010) [101]
			In vitro; Hep3B cells; 12, 25, and 50 M	↓ p38MAPK and ↑ TRAIL-mediated apoptosis; ↓ ERK, ↓ MMP, ↑ caspase-3, caspase-8, and caspase-9 activity, ↑ PARP cleavage, and ↓ Bcl-2 protein	Jin et al. (2009) [39]
			In vitro; Hep G2 cells; 6.75 M baicalein + 25, 50, and 100 M silymarin	↑ cells in G0/G1 phase, ↓ S-phase; ↑ Rb, ↑ p53, ↑ p21(Cip1) and ↑ p27(Kip1), ↓ cyclin D1, ↓ cyclin E, ↓ CDK4, and ↓ phospho-Rb	Chen et al. (2008) [102]
			In vitro/in vivo; MHCC97-H cells/BALB/c nu/nu mice (LCI-D20); 5, 10, and 20 g/mL/50 mg/kg	↑ G(0)/G(1) cell cycle arrest,; ↓ S phase, and ↑ apoptosis ↓ phosphorylation of FAK	Gu et al. (2009) [78]
			In vitro; Hep3B cells; 100 M	↑ ER stress and ↑ mitochondrial insult in Hep3B cells, ↑ m-calpain, ↑ GADD153, ↑ GRP78, and ↑ caspase-12; ↑ caspase-2, ↑ ROS, ↓ Mcl-1	Yeh et al. (2007) [77]

For abbreviations see footer of Table 1.