Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling

Abstract

As a critical factor in the induction of angiogenesis, vascular endothelial growth factor (VEGF) has become an attractive target for anti-angiogenesis treatment. However, the side effects associated with most anti-VEGF agents limit their chronic use. Identification of naturally occurring VEGF inhibitors derived from diet is a potential alternative approach, with the advantage of known safety. To isolate natural inhibitors of VEGF, we established an in vitro tyrosine kinase assay to screen for diet-based agents that suppress VEGFR2 kinase activity. We found that a water-based extract from cinnamon (cinnamon extract, CE), one of the oldest and most popular spices, was a potent inhibitor of VEGFR2 kinase activity, directly inhibiting kinase activity of purified VEGFR2 as well as mitogen-activated protein kinase- and Stat3-mediated signaling pathway in endothelial cells. As a result, CE inhibited VEGF-induced endothelial cell proliferation, migration and tube formation in vitro, sprout formation from aortic ring ex vivo and tumor-induced blood vessel formation in vivo. Depletion of polyphenol from CE with polyvinylpyrrolidone abolished its anti-angiogenesis activity. While cinnamaldehyde, a component responsible for CE aroma, had little effect on VEGFR2 kinase activity, high-performance liquid chromatography-purified components of CE, procyanidin type A trimer (molecular weight, 864) and a tetramer (molecular weight, 1152) were found to inhibit kinase activity of purified VEGFR2 and VEGFR2 signaling, implicating procyanidin oligomers as active components in CE that inhibit angiogenesis. Our data revealed a novel activity in cinnamon and identified a natural VEGF inhibitor that could potentially be useful in cancer prevention and/or treatment.

Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

“…9 There have been several trials of angiogenic therapy applied to different places of cancer formation (breast, prostate, colon, liver, or kidney), [10][11][12][13][14] as well as in the brain. 15,16 Most utilize VEGF (VEGF-A and VEGF-B) or VEGF receptor (VEGFR1-3, PDGFRβ, and c-Kit) inhibition, [17][18][19][20] while some also block pathways not dependent on VEGF (CD36 receptor, FGF pathway, cyclooxygenase-2, and hypoxia-inducible factors 1α) [21][22][23] or inhibit endothelial cell migration (integrins αvβ1, αvβ3, αvβ5). 24 However, up to now, only bevacizumab, containing antiVEGF antibodies, has entered phase III clinical trials for treating GBM.…”

A Comparison of Antimetastatic Activity between Nerium indicum and Cinnamomum burmannii on 4T1 Cells

“…Cinnamaldehyde has Antiinflammatory effect by blocking the degradation of IκB leading to suppression of NF-κB activation (Liao, et al, 2005). Moreover, cinnamaldehyde is an inhibitor of angiogenesis as a natural VEGF inhibitor (Lu, et al, 2010). These results suggested that JLE and CEO showed higher toxicity on 4T1 metastatic breast cancer cells than on cervical cancer cells that could potentially be useful in cancer prevention and/or treatment.…”

“…Jure leaves have been reported as anti-cancer agent since 1980 (Hartwel, 1982), cardiac illnesses, asthma, corns, cancer, and epilepsy (Duke and Boca Raton, 1985) hypertension and also diabetes (Tahraoui, 2007). On the other hand, Cinnamon is potential to be developed as chemopreventive agent because it can be inhibitor of angiogenesis protein (Lu, et al, 2010). It also inhibits many cancer cells growth and induces G2/M phase arrest (Scoene, et al, 2008).…”

Preparative HPLC fractionation of Cinnamomum cassia Water Extract and their in-vitro Antimalarial Activities

“…Cinnamon is one of the well-known and widely used spices which has gained recent attention due to its important medicinal traits. Among the numerous increased health benefits reported on cinnamon are antimicrobial (Matan et al, 2006), antifungal (Wang et al, 2005), antitermitic (Tung et al, 2010(Tung et al, ), nematicidal (park et al, 2005, insecticidal (Cheng et al, 2009), anti-inflammatory (Tung et al, 2008), antioxidant (Mathew and Abraham, 2006), antiulcerogenic (Shiraga et al, 1988), anti-diabetic and anticancer activities (Lu et al, 2010). Moreover, it has been reported to have an influence on neurological disorders such as Parkinson's and Alzheimer's diseases (Petersona et al, 2009).…”