In vitro and in vivo mechanistic study of a novel proanthocyanidin, GC-(4鈫?)-GCG from cocoa tea (Camellia ptilophylla) in antiangiogenesis

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• 作者：Kai-kai Li ; Cheuk-lun Liu ; Jacqueline Chor-wing Tam ; Hin-fai Kwok ; Ching-po Lau ; Ping-chung Leung ; Chun-hay Ko ; Chuang-xing Ye
• 关键词：Antiangiogenesis ; GC-(4&rarr ; 8)-GCG ; HMECs ; Transgenic TG(fli1 ; EGFP)y1/+(AB) zebrafish embryo ; Camellia ptilophylla
• 刊名：Journal of Nutritional Biochemistry
• 出版年：March, 2014
• 年：2014
• 卷：25
• 期：3
• 页码：319-328
• 全文大小：1648 K

文摘

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鈫?)-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鈫?)-GCG in vitro and in vivo, and SU5416 was applied as a positive control. The inhibitory effects of GC-(4鈫?)-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鈫?)-GCG was further verified in vivo. Our results demonstrated that GC-(4鈫?)-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鈫?)-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鈫?)-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鈫?)-GCG might be a potential and promising agent of natural resource to be further developed as an antiangiogenic agent.