Table 2.

The molecular details of anti-angiogenic and anti-metastatic properties of flavonoids

Flavonoids	Mechanism of action (Cytotoxicity profiling)	Ref.
Wogonin	Inhibition of PI3K/Akt/NF-κB pathway and TLR4 pathway, inhibition of VEGF secretion from cancer cells, inhibition of tube formation of HUVECs induced by LPS-treated MCF-7 cells and vascularization in mice (Angiogenesis suppression without apoptosis induction)	[56]
Orientin	Downregulation of MMP-9 and IL-8 via inhibition of PKCα/ERK/AP-1/STAT3 signaling pathway (Inhibition of migration and invasion)	[58]
Kaempferol	Inhibition of VEGF/VEGFR-2 and its downstream signaling cascades PI3K/Akt; MEK; ERK (Inhibition of migration, invasion, and tube formation)	[59]
Quercetin	Inhibition of NF-κB, PKC-δ, ERK1/2 along with AMPK activation, and downregulation of uPA/uPAR, MMP-9 and -2 (Inhibition of migration and invasion)	[60]
Luteolin	Upregulation of TIMP-1 and TIMP-2; Inhibition of PI3K/Akt pathway along with downregulation of MMP-9 and -2 (Apoptosis induction; inhibition of migration and invasion)	[61]

Abbreviations: AMPK, adenosine monophosphate activated protein kinase alpha; AP-1, nuclear translocations of activator protein-1; ERK, extracellular signal regulated kinase; HUVECs, human umbilical vein endothelial cells; IL-8, interleukin-8; LPS, lipopolysaccharide; MEK, mitogen-activated protein kinase kinase; MMP-9, matrix metalloproteinase-9; NF-κB, nuclear factor kappa B; PKCα, protein kinase C alpha; PKC-δ, protein kinase C delta; PI3K, phosphoinositide 3-kinase; STAT3, signal transducer and activator of transcription 3; TIMP-1, tissue inhibitor of metalloproteinase 1;TLR4, Toll-like receptor 4; uPA, urokinase plasminogen activator; uPAR, uPA receptor; VEGF, vascular endothelial growth factor; VEGFR-2, VEGF receptor 2.