Flavonoid phenols

Flavonoid phenols

Since angiogenesis plays a critical role in tumor growth and metastasis, we pay special attention to antiangiogenic therapies. In addition to conventional antiangiogenic therapies based on drugs like Bevacizumab, several natural compounds, including EGCG and polyphenols, have been found to have a strong antiangiogenic effect.



It is a flavone found in a variety of fruits and vegetables, including oranges, parsley, and onions, as well as tea. Although its cancer-preventing benefits are recognized 1, it does not have adequate bioavailability, like most polyphenols, to be able to have a strong effect when ingested organically in vegetables and fruits.

However, Apigenin's anticancer activity is quite potent at pharmaceutical levels, where it has been shown to have anti-proliferative, apoptotic, and cancer-cell invasion and metastasis inhibitory effects in the case of some cancers, including colon cancer 2, prostate cancer 3, breast cancer 4, cervical cancer 5, melanoma 6, etc.

In the case of anti-angiogenesis, like resveratrol, the Apigenin negatively regulates hypoxia-inducible factor-1 (HIF-1) in lung, prostate and pancreatic cancer cell lines 7. Apigenin, like curcumin, inhibits angiogenesis in lung and breast cancer by lowering VEGF expression 8. Apigenin's other anti-angiogenic mechanisms target the signalling pathways of proinflammatory transcription factors NF-κB and COX-2 9. Apigenin also suppresses the phosphorylation of VEGFR-2 10.



In cancer prevention, this isoflavone reduces the risk of occurrence of both hormone-dependent and hormone-independent cancers, including prostate cancer, breast cancer, gastric cancer, colon cancer, non-small cell lung cancer and leukaemia 11.

The antitumor effects of genistein are largely due to its anti-angiogenic action. This soy isoflavone inhibits endothelial cell proliferation, as well as tube migration and formation 12.

Genistein's suppressive effects on MMP-2, as well as those it shares with resveratrol on the hypoxia-inducible factor HIF-1 and the vascular endothelial growth factor VEGF, are thought to be responsible for its anti-angiogenic properties 13. Genistein also blocks angiogenesis by inhibiting the activity of protein tyrosine kinase and the activation of mitogen-activated protein kinase (MAPK) 14.



The powerful antioxidant and anti-inflammatory effects of quercetin make it a champion in cancer prevention 15, including colon cancer, prostate cancer, lung cancer, breast cancer, leukaemia 16, etc. At higher doses, however, quercetin proves to be an unbeatable enemy of cancer. Quercetin's anticancer properties include inhibiting cancer cell invasion, progression, and metastasis, as well as having a strong anti-angiogenic effect 17.

Quercetin affects cell proliferation, migration potential, tube formation capacity, and matrix metalloproteinase (MMP)-2 expression in endothelial cells 18. Quercetin's anti-angiogenic activity is also mediated through the blockage of multiple signalling pathways, ranging from COX-2 inhibition in breast cancer 19 to PI3K/Akt, MAPK/ERK, and NF-κB translocation in glioblastoma 20 and other malignancies.

Like curcumin, in prostate cancer, quercetin negatively regulates endothelial growth factor receptor 2 (VEGFR-2) expression, mediated by the Akt/mTOR/P70S6K pathway 21 and by the positive regulation of the anti-angiogenic factor thrombospondin-1 22. In addition, quercetin directly inhibits VEGF expression in breast cancer 23.

EGCG (epigallocatechin-3-gallate)


Regular consumption of green tea is one of the best known ways to prevent several types of cancer 24. The compound that plays the most important role in cancer prevention, however, is epigallocatechin-3-gallate, abbreviated EGCG.

This green tea extract has been shown to be beneficial in suppressing tumor growth, invasion, metastasis, and apoptosis in several malignancies. These include pancreatic cancer 25, prostate cancer, colon cancer 26, breast cancer 27, cervical cancer 28, etc. No less important, however, is the anti-angiogenic effect of EGCG, perhaps one of the most effective polyphenols in combating tumour angiogenesis.

To begin with, EGCG suppresses the expression of HIF-1, the nuclear transcription factor NFB, and the vascular endothelial growth factor VEGF 29. Following that, studies show an inhibition of the dimerization of VEGF receptors, which play an essential role in angiogenesis 30. Additionally, EGCG negatively regulates the PI3K/Akt signalling pathway, which deactivates the metalloproteinase MMP-9 and the pro-inflammatory factor NF-κB 31. Epigallocatechin-3-gallate suppresses liver metastasis in colorectal cancer by inhibiting the AKT signalling pathway and the expression of the endothelial growth factor receptor 2 VEGFR-2 32.

Major anti-angiogenesis signalling pathways targeted by phytochemicals

Rajasekar, Janani, Madan Kumar Perumal, and Baskaran Vallikannan. "A critical review on anti-angiogenic property of phytochemicals." The Journal of Nutritional Biochemistry 71 (2019): 1-15.
A critical review on anti-angiogenic property of phytochemicals


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29. Gu, Jian-Wei, et al. "EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression." Vascular cell 5.1 (2013): 1-10.
30. Rodriguez, Shaun K., et al. "Green tea catechin, epigallocatechin‐3‐gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex." International Journal of Cancer 118.7 (2006): 1635-1644.
31. Qin, Jie, et al. "Epigallocatechin-3-gallate inhibits bladder cancer cell invasion via suppression of NF-κB mediated matrix metalloproteinase-9 expression." Molecular Medicine Reports 6.5 (2012): 1040-1044.
32. Maruyama, Takehito, et al. "(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer." Oncology reports 31.2 (2014): 625-633