Table 5.
Natural anti-tumor angiogenesis terpenoids and their sources, experimental models and anti-angiogenic mechanisms.
| Category | Name | Source | Experimental model | Anti-angiogenic mechanism | Refs |
|---|---|---|---|---|---|
| Monoterpene | Perillyl alcohol | the essential oils of several plants (lavendin, mints, cherries, etc.) | CAM, HUVECs, BLMVECs, K562 | Inhibits VEGF and Akt pathways | (98) |
| D-limonene rich volatile oil | blood orange (Citrus sinensis (L) Osbeck) | SW480 and HT-29 cells, HUVECs | Reduces the levels of VEGF, MMP-9 expression, inhibits the activation of VEGFR1 | (99) | |
| Cantharidin | Mylabris | Subcutaneous and orthotopic pancreatic xenograft models with PANC-1 cells | Inhibits ERK, JNK, PKC, and NF-κB pathways | (100) | |
| Menthol | Mentha haplocalyx Briq | HepG2 cells | Inhibits the expression of VEGF | (101) | |
| Sesquiterpene | β-elemene | the essential oil of Curcuma zedoaria | Rat aortic ring, Chick embryo chorioallantoic membrane, Melanoma growth and metastasis assay in C57BL/6 mice | Suppresses VEGF pathway | (102) |
| Dehydrocostus lactone | Saussurea lappa and Laurus nobilis | lung cancer cells (A549 and H460 cells), Matrigel plugs were implanted in C57BL/6 mice | Suppresses of HIF-1a, Akt and pAkt, GSK-3β and pGSK-3β, as well as ERK, pERK, mTOR, and p-mTOR | (103) | |
| Inhibits MMP-2 and MMP-9 | |||||
| Umbelliprenin | Different spices of Ferula of umbeliferace | CT26 tumor cells, L929 cells | Inhibits the expression of VEGF, MMP2, MMP-9 and CD31 | (104) | |
| Potentiates immune response by IFN-γ increment and IL-4 decrease | |||||
| Bigelovin | Inula helianthus-aquatica | HCT 116 cells, Orthotopic tumor allografts and experimental metastatic models with colon 26-M01 cells | Interferes IL6/STAT3 and cofilin pathways | (105) | |
| Alantolactone | Inula helenium | HUVECs, human MDA-MB‐231 breast cancer xenograft in mice | Suppresses the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt | (106) | |
| Codonolactone | Atractylodes lancea | HUVECs, EA.hy 926 cells | Inhibits MMPs expression and VEGF secretion by down-regulating BMP/Runx2 activation | (107) | |
| Widdrol | Juniperus chinensis | HUVECs, Human colon adenocarcinoma HT29 cells | Suppresses phosphorylation of VEGFR2, AKT, FAK and eNOS | (108) | |
| Diterpene | Tanshinone IIA | The dried root of Salvia miltiorrhiza Bunge | Human EPCs, CAM, Matrigel plug model | Inhibits EPC angiogenesis through the VEGF, PLC, Akt and JNK signaling pathways | (109) |
| 16-hydroxy-pentandralactone | Vitex cofassus | HUVECs | Inhibits VEGF-stimulated HUVEC proliferation | (110) | |
| Cafestol | Unfiltered coffee | HUVECs | Inhibits the phosphorylation of FAK and Akt and decreases nitric oxide production | (111) | |
| Andrographolide | Andrographis paniculate | HUVECs, A549 Cells | Inhibits MMP-9 expression | (112) | |
| Triptolide | Tripterygium wilfordii | HUVECs, Breast cancer cells (Hs578T and MDAMB231) | Inhibits the ERK1/2-HIF1-α-VEGFA signaling pathway | (113) | |
| Triterpene | Ursolic acid | Many plant foods | Ehrlich ascites carcinoma (EAC) cells, Swiss albino mice with EAC cells | Inhibits VEGF and iNOS expression | (114) |
| Nimbolide | Azadirachta indica leaves | HCT-116, HT-29, Caco-2, CRC cells | Inhibits VEGF and MMP-9 expression | (115) | |
| Koetjapic acid | Sandoricum koetjaoe Merr | rat aortic ring, CAM, HUVECs | Inhibits VEGF expression | (116) | |
| Boswellic acid | Boswellia serrata | Ehrlich ascites carcinoma (EAC) cells, Swiss albino mice with EAC cells | Inhibits VEGF and TNF-α expression | (117) | |
| Betulinic acid | The stembark of Betula ssp. and from many other plants | Human endometrial adenocarcinoma (EA) cells | Inhibits prolidase, HIF-1α and VEGF expressions | (118) |