Table 1.

List of flavonoids with potential anticancer activity against various lung cancer cell lines

Flavonoid	Concentration	Cell line	Mechanisms	Reference
EGCG	20 μM	A549 H1650 H460	Upregulation of TP53 causing growth inhibition	[29]
	5–50 μM	H1299 H460	Increased expression of miR-210, leading to growth inhibition	[30]
	70 μM	H69 H69VP	Reduced tolomerase activity, apoptosis induction, DNA fragmentation, and cell cycle arrest	[31]
	2.5–40 μmol/L	H2122 H358 H460 H1975 H1993	Inhibition of cell proliferation	[32]
5HPMF	16.5 μM	H1299	Apoptosis through activation of caspase-3	[34]
5HHMF	16.5 μM	H1299	Apoptosis through activation of caspase-3	[34]
Genistein	10 μM + 50 ng/mL trichostatin A	A549	Enhanced inhibition of growth and increased apoptosis by increasing TNFR-1 death receptor signalling	[35]
	25 μM	H3255 H1650 H1781	Decreased DNA-binding activity of NF-κB and a reduction in COX-2, pAkt, EGFR and PGE2 expression	[37]
	20–40 μM	SPC-A-1	Cell-cycle arrest, antiproliferation, induction of apoptosis via regulation of genes related to apoptosis	[38]
	15–30 μmol/L	H460	Nullified the NF-κB-inducing activity of cisplatin, docetaxel and doxorubicin increasing cell-growth inhibition and inducing of apoptosis	[39]
Fisetin	5–20 μM	A549	Inhibition of both PI3K/Akt and mTOR signalling through attenuating PI3K protein expression, inhibiting Akt and mTOR phosphorylation	[41]
	1, 5,10 μM	A549	Downregulation of ERK1/2, MMP-2, and u-PA. Inhibition of NF-κB and AP-1 binding. Decrease in the nuclear levels of NF-κB, c-Fos, and c-Jun	[42]
Phloretin	125–150 μg/mL	A549 Calu-1 H838 H520	Decreased proliferation, induction of apoptosis, Bcl-2 expression suppression, increased cleaved-caspase-3 and -9 protein expression, MMP-2 and  -9 downregulation	[43]
	25, 50, 100 and 200 μM	A549	Inhibit migration, increase apoptosis via upregulating ERK, JNK, Bax and P38 MAPK and activating caspase-3 and  -9, and TP53 while downregulating Bcl-2 and NF-κB	[44]
Quercetin	0.74–4.40 μmol/L	A549	Dose-dependent decrease in cell growth and an increase in apoptosis	[45]
Kaempferol	10–140 μM	A549	Dose-dependent antiproliferative activity and impaired metastasis via suppression of EMT	[56]
	25 μM	A549	EMT suppression induced by inhibiting the phosphorylation of Smad3 at Threonine-179 by Akt1	[57]
	30, 50 and 80 μM	H460	Apoptosis via induction caspase-3, AIF, and increasing antioxidant enzymes	[58]
Luteolin	20–80 μM	A549	Cell cycle arrest and inducing apoptosis through activating JNK, increasing Bax, promoting procaspase-9 cleavage, and activating caspase-3	[51]
	25–100 μM	A549	Apoptotic effect and reduction of cell motility and cell migration. Upregulation of caspase-3 and caspase-9, downregulation of Bcl-2, increase in expression of Bax, phosphorylation of mitogen-activated protein kinase and extracellular regulated protein kinase (MEK), and activation of Akt	[52]
	10–100 μM	A549 H460	Inhibition of cell proliferation and increased apoptosis via upregulation of a microRNA (miR-34a-5p) that targets an oncogene (MDM4)	[53]
	20–80 μM	A549 H460	Decrease in cell proliferation by downregulation of the Tyro3, Axl, MerTK (TAM) receptor tyrosine kinases (RTK)	[54]
	20–160 μM	H460	Antiproliferative effects via Sirt1-mediated apoptosis	[55]
Isorhamnetin	16 μM	A549	Inhibition of cellular proliferation and colony formation and an increase in apoptosis via the mitochondria-dependent pathway with caspase activation	[47]
	25 μM	A549	Synergistically increase the antiproliferative and proapoptotic effects of the anticancer drugs via disruption of the mitochondrial membrane potential and activation of caspases and PARP	[48]
Hesperidin	5–50 μM	A549 NCIH358	Inhibition of proliferation and induction of apoptosis via loss of mitochondrial membrane potential, activation of caspase-3, and affecting the fibroblast growth factor and NF-κB signal transduction pathways	[60]
	5–100 μM	H1993	Suppression of cell viability	[61]
Acacetin	1–30 μM	A549	Inhibition of cell viability, invasion and migration via disruption of several signalling pathways and kinases including AP-1, NF-κB, c-Fos, c-Jun, MLK3, MAPK3/6, and p38a MAPK	[62]