Table 1.
Signalling pathways | Subfamily involved in the signalling pathway | Cancer types | Quercetin IC50 |
Target genes | Cell line (s)/in vitro model | Possible mechanisms | Refs. |
---|---|---|---|---|---|---|---|
MAPK (family) signalling | p38 | Oral cancer | 100 µM | MDR1, ABCG2 Hsp27 | SCC25 |
↓ Hsp70 expression changes in EMT ↑apoptosis in drug-resistant cells |
[64] |
p38 ERK JNK |
Hepatocellular carcinoma | 400 µM | – | HepG2 Hep3B |
↓growth, ↓proliferation ↑apoptosis cell cycle arrest in the G1 phase |
[65] | |
p38 JNK ERK |
Gastric cancer | 267 μM | TRPM7 | AGS |
↓growth, ↓proliferation, TRPM7 channel inhibition ↑apoptosis |
[66] | |
p38 ERK1/2 JNK |
Choriocarcinoma | 20, 50, 100 μM | – | JAR JEG3 |
↓proliferation cell cycle arrest in the sub-G1 phase ↑ROS, ↑MMP |
[67] | |
p38 JNK |
Gastric cancer | 20 and 40 µM |
Bcl-2 Bcl-xl Bax |
SGC-7901 MGC-803 |
↓cell viability ↑apoptosis cell cycle arrest in the G2/M phase ↑ROS |
[68] | |
p38 JNK |
Retinoblastoma | 0, 25, 75, and 100 µM |
p27 p21 Caspase-3 Caspase -9 |
Y79 |
↓cell viability cell cycle arrest in the G1 phase ↑apoptosis |
[69] | |
ERK | Esophageal cancer | 0–10 µM |
AP-1 NF-κB, p65 COX-2 |
ESCC |
↓growth ↓proliferation ↓inflammation ↓pre-neoplastic lesion formation by NMBA |
[70] | |
ERK1/2 | Prostate cancer | 40 μM | p38, ABCG2, NF-κB | PC3, LNCaP ARPE-19 |
↓ cell viability ↑apoptosis cell cycle arrest in G1 phase ↓cell migration |
[71] | |
ELK1 MEKK/MAP3K5 | Cervical cancer | 25, 50, 100 µM | Caspases, pro-apoptotic genes | HeLa |
↓growth ↓proliferation ↓colony formation ↑apoptosis ↑cell DNA damage cell cycle arrest in G2/M phase ↓cell migration |
[72] | |
p38 JNK ERK1/2 |
Melanoma | 0–200 µM | Apoptotic genes | A375SM A375P |
↓cell viability ↓growth ↓proliferation ↑morphological and histological changes ↑apoptosis |
[73] | |
p38 JNK ERK1/2 |
Canine osteosarcoma | 0–100 µM | – | D‐17, DSN |
↓proliferation, ↑ MMP, ↑ROS ↓free cytosolic calcium cell cycle arrest in G1 phase |
[74] | |
JAK/STAT (family) | STAT3 | Gastric cancer | 40 μmol/L | Leptin receptor gene | MGC-803 |
↑apoptosis ↑necrosis cell cycle arrest in G2/M phase |
[53] |
JAK1/STAT3 | Glioblastoma | 0–100 µM |
IL-6 cyclin D1, MMP2 |
U87, T98G |
↓ cancer cells growth ↓ IL-6 ↓Rb phosphorylation, ↓cyclin D1 ↓MMP2 ↓cell migration |
[54] | |
STAT1/3 JAK1/2 |
Cholangiocarcinoma | 20–100 µM | iNOS, ICAM-1 | KKU100, KKU-M139 KKU-M213 |
↓STAT1/3 phosphorylation ↓iNOS, ↓ICAM-1 ↓growth, ↓migration ↓activity |
[55] | |
STAT3 | Non-small-cell Lung-cancer | 10–100 μM |
NF-κB, Bcl2 Bax |
A549 H460 |
↓growth ↑apoptosis cell cycle arrest in sub-G1 phase |
[56] | |
JAK1/STAT3 | Breast cancer | 0–100 µM | HER-2, MMP-9 | BT474 |
↓ growth and ↓clonogenic ↑apoptosis ↑STAT3 |
[57] | |
JAK2 STAT3/5 |
Cervical cancer | - | Cyclin D1 Apoptotic proteins | Caski, Hela Siha |
↓ cancer cells proliferation, ↓ migration, ↓invasion, ↑apoptosis, ↑autophagy, ↓xenograft growth and development, cell cycle arrest in G2/M phase |
[58] | |
JAK2/STAT3 | Hepatocellular carcinoma | 80, 120 μmol/L | – | LM3 |
↓tumor cell growth ↓viability ↓migration, ↓invasion ↑autophagy cell cycle arrest in S and G2/M phases |
[59] | |
Wnt/β-catenin | β-catenin/Tcf | Teratocarcinoma | 70 µM | β-catenin, SOX2, Nanog, Oct4 | NT2/D1 | ↓β-catenin nuclear translocation, ↓transcription factors expression | [37] |
DKK1, 2 and 3 | Breast cancer | 10, 20, 40 µM | Apoptotic genes | 4T1 |
↑apoptosis ↓ cancer cell viability |
[38] | |
β-catenin/Tcf | Colon cancer | 40, 80 µmol/L | Cyclin D1, survivin | SW480 |
↑Wnt/β-catenin ↓ cyclin D1, ↓survivin |
[39] | |
β-catenin/ TCF/LEF |
Colon cancer | 10–75 µM | GSK3 α ,GSK3 β | HT29 | the level of β-catenin in HT29 cells remained unaffected | [40] | |
PI3K/Akt | p-Akt | Breast cancer | 25 µM | PTEN | HCC1937 |
↓Akt/PKB phosphorylation ↓cell proliferation |
[43] |
p-Akt PI3K |
Leukaemia | 150 µM |
Bcl-2, Bax, caspase-2 caspase -3 poly (ADP-ribose) polymerase cleavage |
HL-60 |
cell cycle arrest in G (0)/G (1) phase ↑apoptosis |
[44] | |
p-Akt | Gastric cancer stem cell | 20, 100 µM |
Caspase-3 Caspase-9, Bcl2, Cyt-c |
MGC803 | ↑ apoptosis via mitochondrial-dependent pathway and mediated PI3K-Akt signalling pathway | [45] | |
PI3K p-Akt |
Cervical cancer | 25, 50, 100 µM | Bcl-2, Bax | HeLa |
cell cycle arrest in G (0)/G (1) phase, anti-proliferative ↑apoptosis |
[42] |