Table 2.

Antiangiogenic effect of some selected phytochemicals, mentioned in this review.

Name	Structure	Source	Possible Mechanism	References
Damnacanthal	Anthraquinone	Noni	↓VEGFR1-3, c-Met, FAK, FGFR1, 2 and 4 ↓MMP-2, uPA and integrin α5 ↓PI3K-Akt signaling pathway	[351]
Delphinidin	Polyphenol	Grapes, berries, eggplants, red cabbages and tomatoes	↓VEGF-A/VEGFR2 pathway ↓VEGF-A expression ↓PI3K-Akt and ERK signaling pathways	[280,281,282,283,284]
Epigallocatechin gallate	Polyphenol	Teas, berries, kiwis, cherries, pears, peaches, apples, nuts and herbs	↓VEGF-A and MMP-2 expression ↓ VEGF-A/VEGFR2 pathway ↓HIF-1α, NFκB	[363,364,365,366,367,368,369,370,371,372,373,374,375]
Genistein	Polyphenol	Soybeans	↓VEGF-A, PDGF, MMPs expression ↑angiogenesis inhibitors ↓HIF-1α, PI3K/Akt, MAPK, NFκB and Bax/Bcl-2	[194,203,204,205,206,207,208,209]
Hydroxytyrosol	Phenolic alcohol	Tomato, pink grapefruit, oranges and watermelon	↓VEGFR2 phosphorylation and ERK SAPK/JNK pathways ↓MMPs secretion ↓PI3K/Akt and NFκB ↑Caspases 3 and 7 activation	[305,313,314,315,316,317,318,319,320,321,322]
Kaempferol	Polyphenol	Cruciferous vegetables, spinach, onions, leeks, citrus fruits, grapes and herbs	↓VEGF-A expression and secretion ↓HIF-1α, VEGF-A/VEGFR2 pathways ↓PI3K/Akt, mTOR and MEK/ERK	[186,187,188,189,190]
Luteolin	Polyphenol	Oregano	↓VEGF-A/VEGFR2, p38/MAPK and PI3K/Akt/mTOR signaling pathways ↓VEGF-A and MMP-9 expression ↓HIF-1α and STAT3	[413,414,415,416]
Lycopene	Carotenoid	Tomatoes, pink grapefruit, oranges and watermelon	↓MMP-2 and uPA ↓VEGFR2-mediated PI3K/Akt and ERK signaling pathways	[216,217,218,219,220,221]
Myricetin	Polyphenol	Onions, grapes, berries, nuts and herbs	↓VEGF-A/VEGFR2, p38/MAPK and PI3K/Akt/mTOR signaling pathways	[286,287,288,289,290,291]
Piceatannol	Polyphenol	Grapes, berries, peanuts and sugar cane	↓VEGF-A/VEGFR2- mediated pathways	[279]
Quercetin	Polyphenol	Onions, cruciferous vegetables, spinach, apples, berries, nuts, oregano, teas and herbs	↓VEGF-A/VEGFR2, p38/MAPK, Akt, mTOR and P70S6K signaling pathways	[292,293,294,295,296,297,298,299]
Resveratrol	Polyphenol	Grapes and other fruits (mainly berries) and nuts	↓VEGF-A expression ↓HIF-1α, GSK3b/β-catenin/TCF, VEGF-A/VEGFR2 and TFG-β pathways ↓ERK-mediated PKM2 nuclear translocation	[266,267,268,269,270,271,272,273]
Rosmarinic acid	Phenolic acid	Oregano, lemon balm, sage, marjoram and rosemary	↓bFGF/FGFR signaling pathway	[410,411,412]
Sulforaphane	Glucosinolate	Cruciferous vegetables (mainly broccoli)	↓HIF-1α, VEGF-A/VEGFR2 pathways ↓MEK/ERK and PI3K/Akt	[182,183,184]
Tanshinone IIA	Terpenoid	Danshen	↓VEGF-A/VEGFR2 and PI3K/Akt pathways ↓MMP-2 and ↑TIMP-1 levels ↓HIF-1α-mediated β-catenin/TCF3/LEF1 pathway in hypoxia ↓TGF-β1-mediated β-catenin/TCF3/LEF1 pathway in normoxia	[393,394,395,396,397,398]
Ursolic acid	Pentacyclic triterpene	Berries, apples, prunes, elder flower, peppermint, oregano and herbs	↓MMP-2 and 9, ↑TIMP-1 levels ↓VEGF-A, bFGF and iNOS genes expression ↓Activation of SHH, STAT3, Akt and p70S6K pathways	[340,341,342,343,344,345]