Table 2.

The therapeutic effects of quercetin on lung cancer.

Model	Type of Quercetin (Que)	Cell/Animal model	Result	Que Dose	Ref
in vitro	Que	A-549	increased BCL2/BAX mediated apoptosis expression and inhibition of vimentin and N-cadherin (cytoskeletal proteins that function in migration).	10, 30, 60 μM	(95)
in vitro	Que	A-549	downregulate IL-6, STAT-3, Bcl2 activity, NF-κB expression, and upregulate the Annexin and the PI cell population through induction of mitochondrial-mediated apoptosis.	10 – 100 μM	(96)
in vitro	Que	A-549	enhanced TRAIL-induced cell death via autophagy flux activation. Decreased the p62 protein expression and enhanced caspase-3 cleavage.	20, 40, 80 μM	(97)
in vitro	quercetin -metabolite-enriched plasma (QP)	A-549	inhibited cell invasion, Matrix metalloproteinases (MMP-2) activity and migration in dose-dependent effects.	2 – 10 μM	(98)
in vitro	Que	A-549	Reduced mRNA expressions of urokinase plasminogen activator (uPA) and inhibited mRNA expression of CXCL-8, CXCR1, ß-catenin connection to migration and invasion of EMT in lung cancer cells.	20-40 μM	(116)
in vitro	Que	A-549, HCC827	inhibited the migration/invasion of non-small cell lung cancer (NSCLC) cell lines through suppressing the EMT.	10–50 μM	(33)
In vitro	Que	A-549	Inhibited tumorigenesis in human lung cancer partially mediated via the elevation of miR-16 and decrease in claudin-2 expression without involving Akt and ERK1/2.	0, 0.5, 5, 50, 100 μM	(101)
In vitro	Que	GLC-82/R, HTB-182/R	Suppressed the viability and enhanced the radiosensitivity of NSCLC cells via increasing miR-16-5p expression and suppressing WEE1 mRNA expression in a dose- and-time-dependent manner.	50 μM	(103)
In vitro	Que	A-549	inhibited RTKs. CDK6, which supports the growth and viability of various cancer cells	52.35 ± 2.44 μM	(104)
In vitro + in silico	Que	MCF-7, A549	induced apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression.	0–250 μM	(105)
In vivo	Que + curcumin + benzo(a) pyrene (BP)	Male laka mice	enhanced chemopreventive potential against development of lung carcinogenesis by stimulating the apoptotic machinery. decreased BCL-2 expression and improved BAX protein expression in lung cancer cells.	40 mg/kg	(109)
In vitro + in vivo	Que-loaded mixed micelles (Que-MMICs)	nude BALB/c mice	induced apoptosis and arrested cell cycle in NSCLC and A549 tumor xenograft model established.	0-50 μg/ml	(110)
In vitro + in vivo	YYQFT	C57BL/6 mice	inhibited growth tumor related to high-dose quercetin. decreased BCL-2 expression and improved p53, Fas, Bax and Bag expression in lung cancer cells.	200 μg/ml	(106)
In vitro + in vivo	Que + SBA-15	A-549	Induced cell death via PI3K/AKT/mTOR signaling pathway and increased mTOR, caspase 9, and cytochrome c	0, 20, 40, 80, 100 μg/ml	(117)
In vitro	Que+ TSA	A-549, HCC827	inhibited the migration/invasion of NSCLC cells through suppressing the EMT. suppressed snail-dependent Akt activation by upregulating maspin.	1–100 μM	(111)
In vitro	Que + PTX	A-549, A-549/Taxol	Combination of quercetin and PTX suppressed cell growth and induced apoptosis. Que reversed PTX resistance of lung cancer cells by inhibiting the phosphorylation of Akt and ERK.	0, 5, 10, 20, 40, 80 μg/ml	(118)
In vitro	Que + gemcitabine	A-549, H460	Reduced cell viability and suppressed HSP70 expression in both cell lines dose-dependently.	10, 50, 100, 200 μM	(119)
In vitro + in vivo	Que + PMX	A-549	showed concentration-dependent synergistic inhibitory effects on cancer cell proliferation/migration.	20 µg/mL	(115)

Note: Mesoporous silica nanoparticles (SBA-15); Trichostatin A (TSA); (Polymeric microspheres, PMs), PMs loaded with paclitaxel (PTX); Pemetrexed (PMX).