In vitro and in vivo mechanistic study of a novel proanthocyanidin, GC-(4’8)-GCG from cocoa tea (Camellia ptilophylla) in antiangiogenesis
- Authors
- Li, K.K., Liu, C.L., Tam, J.C., Kwok, H.F., Lau, C.P., Leung, P.C., Ko, C.H., and Ye, C.X.
- ID
- ZDB-PUB-140502-17
- Date
- 2014
- Source
- The Journal of Nutritional Biochemistry 25(3): 319-328 (Journal)
- Registered Authors
- Keywords
- Antiangiogenesis, Camellia ptilophylla, GC-(4’8)-GCG, HMECs, Transgenic TG(fli1:EGFP)y1/+(AB) zebrafish embryo
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology*
- Cacao/chemistry*
- Cell Line
- Humans
- In Vitro Techniques
- Proanthocyanidins/pharmacology*
- PubMed
- 24524904 Full text @ J. Nutr. Biochem.
Angiogenesis, the process of blood vessel formation, is critical to tumor growth. Ant-angiogenic strategies demonstrated importance in cancer therapy. Cocoa tea (Camellia ptilophylla), a naturally decaffeinated tea commonly consumed as a healthy drink in southern China, had recently been found to be a potential candidate for antiangiogenesis. A novel proanthocyanidin, GC-(4→8)-GCG, which consisted of gallocatechin and gallocatechin 3-O gallate moieties, was discovered and thought to be one of the effective candidates for antiangiogenesis. Hence, the present study aimed to evaluate the antiangiogenesis activities of GC-(4→8)-GCG in vitro and in vivo, and SU5416 was applied as a positive control. The inhibitory effects of GC-(4→8)-GCG on three important processes involved in angiogenesis, i.e., proliferation, migration and differentiation, were examined using human microvascular endothelial cell line HMEC-1 by MTT assay, scratch assay and tube formation assay, respectively. Using transgenic zebrafish embryos TG(fli1:EGFP)y1/+(AB) as an animal model of angiogenesis, the antiangiogenic effect of GC-(4→8)-GCG was further verified in vivo. Our results demonstrated that GC-(4→8)-GCG significantly inhibited migration (P<.001) and tubule formation (P<.001–.05) of HMEC-1 in dose-dependent manner. Regarding intracellular signal transduction, GC-(4→8)-GCG attenuated the phosphorylation of ERK, Akt and p38 dose-dependently in HMEC-1. In zebrafish embryo, the formation of new blood vessels was effectively inhibited by GC-(4→8)-GCG in a dose-dependent manner after 3 days of treatment (P<.001–.05). In conclusion, these results revealed that our novel proanthocyanidin, GC-(4→8)-GCG might be a potential and promising agent of natural resource to be further developed as an antiangiogenic agent.