TABLE 5.
Studies on the therapeutic effects of quercetin in HCC.
| Type of Quercetin | Dose | Targets | Results | Model (in vitro/in vivo/Human) | Cell Line | Reference |
|---|---|---|---|---|---|---|
| Quercetin | 100 mg/kg | CK2α, Notch1, Gli2, caspase-3, p53, cyclin-D1, and Ki-67 | Antiproliferation, antioxidant, and antiapoptosis | In vivo | — | Salama et al. (2019) |
| Quercetin | 100–300 μg/ml | — | Prevented CCl4-induced cytotoxicity | In vitro | HepG2 | Vijayakumar et al. (2019) |
| Quercetin | 0–200 µM | JAK2 and STAT3 | Antiproliferation, cell cycle arrest, induced apoptosis, anti-migration, and anti-invasion | In vitro and in vivo | LM3 | Wu et al. (2019a) |
| QRC/SPC co-loaded NCs | 0–100 µM | kappa B, TNF-α, and Ki-67 | Enhancing SFB antitumor efficacy.(antiproliferative and anti-vascularization) | In vivo and In vitro | HepG2 | Abdelmoneem et al. (2019) |
| Quercetin | 12.5–50 µM | Hexokinase-2 and AKT/mTOR | Antiproliferative effect | In vitro and In vivo | SMMG-7721 and BEL-7402 | Wu et al. (2019b) |
| Quercetin | 0–80 μM | AKT/mTOR and MAPK | Autophagy stimulation and Induced apoptosis | In vitro | MMC7721 | Ji et al. (2019) |
| In vivo | HepG2 | |||||
| Quercetin | 0, 20, 40, and 80 µM | Intracellular ROS, p53 | Antiproliferative effect | In vitro | HepG2 | Jeon et al. (2019) |
| Ziziphus spina-christi (ZSCL) | 100 and 300 mg/kg | Hepatocyte growth factor | Antioxidant effects and anti-oncogenic effects | In vivo | HepG2 | El-Din et al. (2019) |
| Insulin-like growth factor-1 receptor | In vitro | |||||
| Quercetin, dasatinib | 5, 50 mg/kg | SASP, P16, and γH2AX foci | Pro-tumorigenic effects | In vivo | HepG2 and Huh-7 | Kovacovicova et al. (2018) |
| In vitro | ||||||
| QCT-SPION-loaded micelles | 0–60 µM | — | Increased cytotoxicity, cell cycle arrest, and antiproliferation | In vitro | HepG2.2.15 | Srisa-Nga et al. (2019) |
| Quercetin | 20–160 μM | Cyclin A, B2, D1, Bcl-2, caspase-3, and -9 | Antiproliferation and induced apoptosis | In vitro | Hep3b and HepG2 | Bahman et al. (2018) |
| Nanocarriers of quercetin | 1, 550, and 150 µM | Caspase-3, H2O2, c-MET, and MCL-1 | Induced apoptosis | In vitro | HepG2 and HeLa | AbouAitah et al. (2018) |
| Quercetin | 40, 80, and 160 μM | ABCB1, ABCC1, ABCC2, and Wnt | Enhanced sensitivity and increased cellular accumulation of chemotherapy drugs | In vitro | BEL/5-FU | Chen et al. (2018) |
| BEL-7402 | ||||||
| Quercetin (SFJDC) | 6.75 μg/ml | Bcl-2, Bax, Akt/mTOR, and NF-κB | Induced apoptosis, inhibited migration and invasion, affected, af | In vitro | HepG2 HepG2.2.15 | Xia et al. (2018) |
| Quercetin | 0–100 μM | p38, MAPK, JNK, and MEK1 | Induced apoptosis | In vitro | HepG2 | Ding et al. (2018) |
| Quercetin | 5–50 μM | NF-κB | Enhanced Antiproliferative effects and induced apoptosis | In vitro | SMMC-7721 | Zou et al. (2018) |
| In vivo | HepG2, HuH-7 | |||||
| Quercetin | 10, 25, and 50 μΜ | JAK, SHP2 phosphatase, and IFN-α | Antiproliferative effect | In vitro | HepG2 Huh7 | Igbe et al. (2017) |
| 3′,4′,7-Tri-O quercetin | 25 mg | — | Stability indicator for hydrolytic degradation | In vivo | — | Bianchi et al. (2018) |
| 3′,4′,5,7-Tetra-Oquercetin | 29.9 mg | — | Stability indicator for hydrolytic degradation | In vivo | — | Bianchi et al. (2018) |
| 3′,4′-Di-O quercetin | 38 mg | — | Stability indicator for hydrolytic degradation | In vivo | — | Bianchi et al. (2018) |
| Quercetin + maleic anhydride derivatives | 50 mM | ROS, caspase-3, -9, and cytoskeletal actin | Cytotoxic effect, Induced apoptosis, Cell cycle arrest, and modification in cytoskeletal actin and nucleus morphology | In vitro | HuH7, HepG2 | Carrasco-Torres et al. (2017) |
| Quercetin | 25 μg/ml | IGF2BP1, 3, and miR-1275 | Reduced viability | In vitro | Huh-7 | Shaalan et al. (2018) |
| nano prototype + quercetin | 0.10, 20, 50, and 100 mM | IC50s | Induced Apoptosis, necrosis, and antiproliferative effects | In vitro | HepG2 | Abd-Rabou and Ahmed (2017) |
| Quercetin-3-O-rutinosidequercetin, -glucoside | 2.5–100 μg/ml | — | Cytotoxic effects against cancer cells | In vitro | HEPG2 | Sobral et al. (2017) |
| Quercetin | 0.67 μM | — | Weak cytotoxic effects against cancer cells and antioxidant effects | In vitro | HepG2, Hep3B | Ma et al. (2017) |
| Quercetin | 100 mg/kg | HSP70 | Induced apoptosis | In vivo | Ma et al. (2017) | |
| Quercetin nanoparticlee | 1–50 μM | — | Inhibited tumor growth effect | In vivo | HepG2 | Wang et al. (2016a) |
| In vitro | ||||||
| Quercetin | 6.25–100 μM | HDAC8 | Cytotoxic effects | In vitro | HepG2 | Mira and Shimizu (2015) |
| Quercetin | 5–200 µM | GLUT-1 and BAX/BCL-2 | Induced apoptosis | In vitro | HepG2, HuH7, and Hep3B2.1–7 | Brito et al. (2016) |
| Quercetin | 40 mg/kg | Bad, Bax, Bcl-2, and survivin | Induced apoptosis, enhanced 5-FU efficacy, and antiproliferative effects | In vitro and In vivo | HepG2 and SMCC-7721 | Dai et al. (2016) |
| Quercetin-3-O-glucoside | 20–500 μg/ml | — | Antioxidant, cytotoxicity, and induced apoptosis | In vitro | HepG2 | C. Maiyo et al. (2016) |
| Quercetin | 0–100 µM | PI3K, PKC, ROS, COX-2, p53, and BAX | Cytotoxicity and anticarcinogenic actions | In vitro | HepG2 | Maurya and Vinayak (2015) |
| Quercetin | 0–50 µM | F-actin | Induced apoptosis and cell cycle arrest | In vitro | HepG2 | Pi et al. (2016) |
| Quercetin-3-O-glucoside | 100 µM | Caspase-3 and DNA topoisomerase II | Antiproliferative effects, cell cycle arrest, and induced apoptosis | In vitro | HepG2 | Sudan and Rupasinghe (2015) |
| Quercetin | 0–100 µM | Specificity protein 1 (Sp1) | Induced apoptosis and antiproliferative effects | In vitro | HepG2 | Lee et al. (2015c) |
| Quercetin-3-O-glucoside | 1–200 μM | Human DNA topoisomerase II and caspase-3 | Antiproliferative effects, antioxidant effects, cell cycle arrest, and induced apoptosis | In vitro | HepG2 | Sudan and Rupasinghe (2014) |
| Nanocapsulated quercetin | 8.98 μmol/kg | TNF-α, IL-6, and MMP-13 | Controlled diethylnitrosamine-induced carcinoma | In vivo | — | Mandal et al. (2014) |
| Quercetin | 1, 5, 10, 20, and 50 mM | — | Cytotoxicity | In vitro | HepG2 | Varshosaz et al. (2014) |
| Quercetin | 1–50 mM | — | Anticancer effects | In vitro | HepG2 | Varshosaz et al. (2014) |
| Quercetin | 1–50 mM | — | Anticancer effects | In vitro | HepG2 | Varshosaz et al. (2014) |
| Quercetin | 50 μM | P16 | Antiproliferative effects and induced apoptosis | In vitro | HepG2 | Zhao et al. (2014) |
| Quercetin | 1–10 μg/ml | - | Cytotoxicity | In vitro | HepG2 | Mohamed Al-Taweel et al. (2012) |
| Quercetin | 5 μg/ml | - | Anti-inflammatory and antioxidant | In vitro | HepG2 | Isa et al. (2012) |
| Quercetin | 50 μmol/L | Heat shock proteins-90, 70, 90α, 76, 60, aand 27 | Antiproliferation and inhibited all heat shock proteins | In vitro | HepG2 | Zhou et al. (2011) |
| Quercetin | 50 μM | Akt, pAkt, Bcl-2, caspase-3, and -9 | Induced apoptosis | In vitro | HepG2 and Hep3B | Sharma and Bhat (2011) |
| Quercetin + BB-102 | 3.125–100 μmol/L | p53, GM-CSF, and B7-1 | Antiproliferation and induced apoptosis | In vitro | BEL-7402, HuH-7, and HLE | Shi et al. (2003) |
| Nanoliposomal quercetin | 100 mg/kg/d | — | Induced apoptosis and inhibited formation of malignant ascites | In vivo | — | Yuan et al. (2006) |
| Quercetin dissolved in DMSO | 0, 40, 60, or and 80 μM | — | Enhanced apoptotis cell cycle arrest | In vitro | HA22T/VGH HepG2 | Chang et al. (2006) |
| Quercetin and/or Ni nanoparticles | 5.0, 25 and 50 μmol/L | — | Antiproliferative effects | In vitro | SMMC-7721 | Guo et al. (2009) |
| Quercetin | 0–200 µM | DR5, c-FLIP, and Bcl-xL | Recovered TRAIL sensitivity and induced apoptosis | In vitro | HepG2, SK-Hep1, SNU-387, and SNU-449 | Kim et al. (2008) |
| ANBE includes quercetin | 100 and 200 mg/kg | CAT, SOD, GPx, GST, ALT, ALP, TBL, AFP, and CEA | Antioxidant effects and induced apoptosis | In vivo | — | Singh et al. (2009) |
| Quercetin | 200 mg/kg | p53 | Decreased oxidative stress | In vivo | — | Seufi et al. (2009) |
| Quercetin | 40 and 80 μM | SOD and MnSOD | Antiproliferative effects and induced apoptosis | In vitro | HA22T/VGH HepG2 | Chang et al. (2009) |
| Quercetin | 22 µL | p27(Kip1) | Induced apoptosis, cell cycle arrest, and inhibited topoisomerase IIα activity | In vitro | HepG2 | Naowaratwattana et al. (2010) |
| Quercetin | 0–100 μM | CYP1A1 | Increase cytotoxicity, protective effect against DNA strand breaks, and antioxidant activity | In vitro | HepG2 | Kozics et al. (2011) |
| Quercetin, nanoencapsulated quercetin | 8.98 and 1.898 mmol/ml | Cytochrome c | Antiproliferative effects, antioxidant activity, and induced Apoptosis | In vivo | — | Ghosh et al. (2012) |
| Quercetin | 8 μg/ml | PI3K-AKT | Inhibited proliferation | In vitro | HepG2 and Huh-7 | Pan and Pan (2021) |
| Quercetin | 50 mg/kg | P16 | Ineffective against age-associated NAFLD-induced HCC | In vitro and In vivo | DEN/HFD mouse model | Raffaele et al. (2021) |
| Quercetin | 100 μg/ml | PEPCK and G6Pase | Antioxidant effect | In vitro | HepG2 | Pasachan et al. (2021b) |
| Quercetin | 100 mg/kg | Nrf2/Keap1 pathway | Antioxidant effect | In vitro and in vivo | HepG2 and male Kunming mice | Zhang et al. (2020) |
| Quercetin | 100 μM | — | Antiproliferative effect, induced apoptosis, G0/G1, G2/M, and S phase cell cycle arrest | In vitro | KIM-1, HAK-1A, HAK-1B, HAK-2, and HAK-3 | Hisaka et al. (2020) |
| Quercetin | 3, 7 μM | TGF-α, p38 MAPK, and AKT | Suppressed migration | In vitro | HuH7 | Yamada et al. (2020) |