Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-Forming Endothelial Cells through Inactivation of Survival Signal ERK1/2.
Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-Forming Endothelial Cells through Inactivation of Survival Signal ERK1/2.
复制标题
DOI：
10.1093/ecam/nep024
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Kunimasa K;Ahn MR;Kobayashi T;Eguchi R;Kumazawa S;Fujimori Y;Nakano T;Nakayama T;Kaji K;Ohta T
我们最近报道，顺铂抑制肿瘤诱导的血管生成通过管形成抑制和诱导内皮细胞凋亡。然而，这种血管生成抑制的分子机制还没有完全阐明。本研究的目的是研究巴西枸杞乙醇提取物（EEBP）对两个主要的生存信号，细胞外信号调节激酶1/2（ERK 1/2）和Akt的影响，并阐明这些信号的变化是否实际上参与了巴西枸杞的抗血管生成作用。Western blotting检测显示EEBP抑制ERK 1/2的磷酸化，但不抑制Akt的磷酸化。U 0126的药理学抑制表明，单独的ERK 1/2失活足以抑制管形成并诱导凋亡。还显示EEBP和U 0126类似地诱导半胱天冬酶-3的活化和聚ADP-核糖聚合酶（PARP）和核纤层蛋白A/C的裂解，所有这些都是细胞凋亡的分子标志物。这些结果表明，抑制生存信号ERK 1/2，并随后诱导细胞凋亡，是一个重要的机制，血管生成抑制EEBP。
We recently reported that propolis suppresses tumor-induced angiogenesis through tube formation inhibition and apoptosis induction in endothelial cells. However, molecular mechanisms underlying such angiogenesis suppression by propolis have not been fully elucidated. The aim of this study was to investigate the effects of ethanol extract of Brazilian propolis (EEBP) on two major survival signals, extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt, and to elucidate whether changes in these signals were actually involved in antiangiogenic effects of the propolis. Detection by western blotting revealed that EEBP suppressed phosphorylation of ERK1/2, but not that of Akt. Pharmacological inhibition by U0126 demonstrated that ERK1/2 inactivation alone was enough to inhibit tube formation and induce apoptosis. It was also shown that EEBP and U0126 similarly induced activation of caspase-3 and cleavage of poly ADP-ribose polymerase (PARP) and lamin A/C, all of which are molecular markers of apoptosis. These results indicate that inhibition of survival signal ERK1/2, and subsequent induction of apoptosis, is a critical mechanism of angiogenesis suppression by EEBP.
登录
查看更多内容
DOI：
10.1093/ecam/neh034
发表时间：
2004-09-01
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Chen CN;Weng MS;Wu CL;Lin JK
通讯作者：
Lin JK
影响因子：
3.4
作者：
Castaldo, S;Capasso, F
通讯作者：
Capasso, F
影响因子：
5.4
作者：
Banskota, AH;Tezuka, Y;Kadota, S
通讯作者：
Kadota, S
影响因子：
9.7
作者：
Kondo, T;Ohta, T;Kaji, K
通讯作者：
Kaji, K
影响因子：
2
作者：
Miyataka, H;Nishiki, M;Satoh, T
通讯作者：
Satoh, T