Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets

Asgharian, Parina; Tazekand, Abbas Pirpour; Hosseini, Kamran; Forouhandeh, Haleh; Ghasemnejad, Tohid; Ranjbar, Maryam; Hasan, Muzaffar; Kumar, Manoj; Beirami, Sohrab Minaei; Tarhriz, Vahideh; Soofiyani, Saiedeh Razi; Kozhamzharova, Latipa; Sharifi-Rad, Javad; Calina, Daniela; Cho, William C.

doi:10.1186/s12935-022-02677-w

Cancer Cell International

Table 1 The role of quercetin in various cancers mediated by signalling pathways—evidence from preclinical studies

From: Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets

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]

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