Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells.
Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells.
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DOI：
10.1111/j.1349-7006.2002.tb01273.x
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发表时间：
2002-04
期刊：
影响因子：
--
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Kwon HJ;Shim JS;Kim JH;Cho HY;Yum YN;Kim SH;Yu J
桦木酸（BetA）是一种五环三萜，是一种直接在线粒体中起作用的选择性凋亡诱导剂。最近的研究表明，BetA抑制氨肽酶N（APN，EC 3.4.11.2）的体外酶活性，已知氨肽酶N在血管生成中起重要作用，但BetA的抗血管生成活性尚未报道。本文提供的数据表明，BetA在对细胞活力无影响的浓度下有效抑制碱性成纤维细胞生长因子（bFGF）诱导的牛主动脉内皮细胞（BAEC）的侵袭和管形成。为了评估BetA的抗血管生成性质是否源于其对氨肽酶N（APN）活性的抑制作用，研究了BetA对APN的影响。令人惊讶的是，BetA在内皮细胞或APN阳性肿瘤细胞中不抑制体内APN活性。另一方面，BetA显著降低了线粒体还原电位，并且用线粒体通透性转换（MPT）抑制剂处理减弱了BetA诱导的内皮细胞侵袭抑制。这些结果表明，BetA的抗血管生成活性是通过调节内皮细胞中的线粒体功能而不是APN活性而发生的。
Betulinic acid (BetA), a pentacyclic triterpene, is a selective apoptosis‐inducing agent that works directly in mitochondria. Recent study has revealed that BetA inhibits in vitro enzymatic activity of aminopeptidase N (APN, EC 3.4.11.2), which is known to play an important role in angiogenesis, but the anti‐angiogenic activity of BetA has not been reported yet. Data presented here show that BetA potently inhibited basic fibroblast growth factor (bFGF)‐induced invasion and tube formation of bovine aortic endothelial cells (BAECs) at a concentration which had no effect on the cell viability. To access whether the anti‐angiogenic nature of BetA originates from its inhibitory action against aminopeptidase N (APN) activity, the effect of BetA on APN was investigated. Surprisingly, BetA did not inhibit in vivo APN activity in endothelial cells or APN‐positive tumor cells. On the other hand, BetA significantly decreased the mitochondrial reducing potential, and treatment with mitochondrial permeability transition (MPT) inhibitors attenuated BetA‐induced inhibition of endothelial cell invasion. These results imply that anti‐angiogenic activity of BetA occurs through a modulation of mitochondrial function rather than APN activity in endothelial cells.
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影响因子：
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作者：
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