Table 1.

The role of quercetin in various cancers mediated by signalling pathways—evidence from preclinical studies

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]