Theaflavin-3, 3'-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and Notch-1 pathways, not via MAPK pathways.
Theaflavin-3, 3'-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and Notch-1 pathways, not via MAPK pathways.
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DOI：
10.3892/ijo.2015.3257
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发表时间：
2016-01
影响因子：
5.2
通讯作者：
Chen YC
中科院分区：
文献类型：
--
作者：
Gao Y;Rankin GO;Tu Y;Chen YC
茶黄素-3，3 ′-二没食子酸酯（TF 3）是由新鲜茶叶发酵过程中的绿色茶多酚表儿茶素没食子酸酯和（−）-表没食子儿茶素-3-没食子酸酯（EGCG）聚合和氧化产生的红茶多酚。据报道，TF 3具有抗癌特性。然而，TF 3对肿瘤血管生成的影响及其机制尚不清楚。在本研究中，TF 3被证实抑制肿瘤血管生成。与EGCG相比，TF 3的作用更强。TF 3在人脐静脉内皮细胞模型和鸡胚绒毛尿囊膜模型中抑制人卵巢癌OVCAR-3细胞诱导的血管生成。TF 3通过下调HIF-1α和VEGF的表达而抑制肿瘤血管生成。TF 3失活Akt/mTOR/p70 S6 K/4 E-BP 1通路和Akt/c-Myc通路是其作用机制之一。TF 3抑制Notch-1的切割，降低c-Myc、HIF-1α和VEGF的表达，最终诱导受损的肿瘤细胞血管生成。然而，TF 3对MAPK通路没有任何影响。总之，这些发现表明TF 3可能作为一种潜在的抗血管生成剂用于癌症治疗。
Theaflavin-3, 3′-digallate (TF3) is a black tea poly-phenol produced from polymerization and oxidization of the green tea ployphenols epicatechin gallate and (−)-epigallocatechin-3-gallate (EGCG) during fermentation of fresh tea leaves. TF3 has been reported to have anticancer properties. However, the effect of TF3 on tumor angiogenesis and the underlying mechanisms are not clear. In the present study, TF3 was verified to inhibit tumor angiogenesis. Compared with EGCG, TF3 was more potent. TF3 inhibited human ovarian carcinoma OVCAR-3 cell-induced angiogenesis in human umbilical vein endothelial cell model and in chick chorioallantoic membrane model. TF3 reduced tumor angiogenesis by downregulating HIF-1α and VEGF. One of the mechanisms was TF3 inactivated Akt/mTOR/p70S6K/4E-BP1 pathway and Akt/c-Myc pathway. Besides, TF3 suppressed the cleavage of Notch-1, subsequently decreased the expression of c-Myc, HIF-1α and VEGF, and finally the impaired cancer cells induced angiogenesis. Nevertheless, TF3 did not have any influence on the MAPK pathways. Taken together, these findings suggest that TF3 might serve as a potential anti-angiogenic agent for cancer treatment.