Table 2.
Natural anti-tumor angiogenesis polyphenols and their sources, experimental models and anti-angiogenic mechanisms.
| Category | Name | Source | Experimental model | Anti-angiogenic mechanism | Refs |
|---|---|---|---|---|---|
| Hydroxybenzoic acid derivative | Ellagic acid | blackberry | ECV304 cell line, Hamster cheek pouch carcinogenesis model, HUVEC cells | Inhibits VEGFR2 expression | (39, 40) |
| Inhibits VEGF/VEGFR2, PI3K/Akt and MAPK signaling cascades | |||||
| Hydroxycinamic acid derivatives | Chlorogenic acid | Eucommia ulmoides Oliv | A549 cells | Suppresses HIF-1α/Akt pathway | (41) |
| Curcumin | Curcuma aromatica Salisb | A549 and PC-9 cells, Nude mice xenograft tumor model, T24 and UMUC2 cells, HUVEC cells | Blocks c-Met expression and PI3K/Akt/mTOR pathway | (42–44) | |
| Blocks IGF2 and IGF2 mediated PI3K/AKT/mTOR Signaling Pathway | |||||
| Cyclic nucleotide phosphodiesterases inhibition | |||||
| Flavonols | Quercetin | Quercus iberica | MCF-7 cells, BALB/c nude mice xenograft model, HUVEC cells, Transgenic zebrafish embryos TG | Inhibits calcineurin/NFAT pathway, Inhibits ERK phosphorylation and VEGFR-2 expression | (45, 46) |
| Flavanols | Catechin | black tea | HUVEC and HASMC cells | Inhibits VEGF expression | (47) |
| Theaflavin | black tea | OVCAR-3 and A2780/CP70, HUVEC | TF1 reduces VEGF secretion in a HIF1α-independent manner, while the others in a HIF1α-dependent way | (48) | |
| (-)-epigallocatechin gallate | green tea | SW620, HT-29, HCT116, Endothelial cells and xenografts | Suppresses JAK/STAT3/IL-8 pathway and VEGFR2 expression | (49, 50) | |
| Flavones | Baicalin | Scutellaria baicalensis Georgi | A549 cell, Xenograft tumors in nude mice | VEGFR expression inhibition | (51) |
| Apigenin | Apium graveolens L.var.dulce DC. | PC3-M and LNCaP C4-2B cells | Blocks TGF-β1-Smad-VEGF pathway | (52) | |
| Luteolin | Reseda odorata L. | Sprague-Dawley rat | VEGF expression inhibition | (53) | |
| Eupatorin | Isatis tinctoria | HUVEC cells | VEGF expression inhibition | (54) | |
| xanthomicrol | Citrus reticulata Blanco | HUVEC cells and rat aortic rings | VEGF expression inhibition | (55) | |
| calycopterin | Dracocephalum kotschyi | HUVEC cells and rat aortic rings | VEGF expression inhibition | (55) | |
| Anthocyanins | Delphinidin | Pharbitis nil(L.)Choisy | A549 cell | Inhibits HIF-1α and VEGF expression | (56) |
| Cyanidin | purple sweet potato | HUVEC and HRMEC | Blocks ERK pathways | (57) | |
| Peonidin | lycium ruthenicum | HUVEC and HRMEC cells | Blocks ERK pathways | (57) | |
| Malvidin | Malva sinensis Cavan. | SCC131 cells | Suppresses JAK/STAT-3 pathway | (58) | |
| Isoflavone | 6-methoxyequol | soybean | HUVECs A431 cells, Mouse xenograft tumors model | Suppresses MAPK pathway | (59) |
| Pyranoisoflavone | Barbigerone | soybean | B16F10 melanoma cells, Zebrafish and mouse xenograft tumors models | Suppresses MEK 3/6/p38 MAPK signaling pathway | (60) |
| Chalcone | Cardamonin | Alpinia katsumadaiHayata | SKOV3 cells | Inhibis VEGF and HIF-α expression | (61) |
| Xanthohumol | Humulus lupulus L. | BxPC-3 cells | Blocks NF-κB expression | (62) | |
| Biflavonoid | Amentoflavone | Selaginella tamariscina | TSGH8301 cell | Suppresses VEGF expression | (63) |
| Hinokiflavone | Platycladus orientalis (Linn.) Franco | CT26 cell | – | (64) | |
| Stilbens | Resveratrol | Peanut | Rats | MMP-9 expression inhibition | (65) |