title: In vitro and in vivo mechanistic study of a novel proanthocyanidin, GC-(4→8)-GCG from cocoa tea (Camellia ptilophylla) in antiangiogenesis.
abstract: 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.
authors: Department of Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Kai-kai
authors: KK
authors: Li
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
authors: Cheuk-lun
authors: CL
authors: Liu
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
authors: Jacqueline Chor-wing
authors: JC
authors: Tam
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
authors: Hin-fai
authors: HF
authors: Kwok
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
authors: Ching-po
authors: CP
authors: Lau
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China; The Chinese University of Hong Kong Shenzhen Research Institute.
authors: Ping-chung
authors: PC
authors: Leung
authors: Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China; The Chinese University of Hong Kong Shenzhen Research Institute. Electronic address: gohey@cuhk.edu.hk.
authors: Chun-hay
authors: CH
authors: Ko
authors: Department of Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Chuang-xing
authors: CX
authors: Ye
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002099:Cacao / Q000737:chemistry*; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D044945:Proanthocyanidins / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D044945:Proanthocyanidins
keywords: Antiangiogenesis; Camellia ptilophylla; GC-(4→8)-GCG; HMECs; Transgenic TG(fli1:EGFP)y1/+(AB) zebrafish embryo