A new terrein glucoside, a novel inhibitor of angiogenin secretion in tumor angiogenesis
A new terrein glucoside, a novel inhibitor of angiogenin secretion in tumor angiogenesis
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DOI：
10.1038/ja.2008.60
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发表时间：
2008-07-01
影响因子：
3.3
通讯作者：
Ikeda, Daishiro
中科院分区：
文献类型：
--
作者：
Arakawa, Masayuki;Someno, Tetsuya;Ikeda, Daishiro
血管生成是肿瘤治疗的关键步骤。许多血管生成因子参与肿瘤血管生成。在我们筛选血管生成素分泌抑制剂（血管生成因子之一）的过程中，我们从真菌菌株曲霉菌的发酵液中分离出新的土曲霉糖苷（1）和土曲霉素（2）。 PF1381。根据光谱和酶分析，I的结构和绝对立体化学被确定为(4S,5R)-5-[(α-D-吡喃葡萄糖基)氧基]-4-羟基-3-(E-1-丙烯基)-2-环戊烯-1-酮。化合物I和2同样抑制雄激素依赖性前列腺癌细胞LNCaP-CR的血管生成素分泌，IC 50 值为13μM。然而，两种化合物不影响另一种血管生成因子VEGF的分泌。此外，这两种化合物都能抑制人脐静脉内皮细胞（HUVEC）的管形成。这些结果表明1和2通过抑制血管生成素分泌而充当血管生成抑制剂。
Angiogenesis is a critical step for the tumor therapy. Many angiogenic factors are involved in the tumor angiogenesis. In the course Of Our screening for inhibitors of angiogenin secretion, one of angiogenic factors, we have isolated a new terrein glucoside (1) and terrein (2) from the fermentation broth of fungal strain Aspergillus sp. PF1381. The structure and absolute stereochemistry of I was determined to be (4S,5R)-5-[(alpha-D-glucopyranosyl)oxy]-4-hydroxy-3-(E-1-propenyl)-2-cyclopenten-1-one on the basis of spectral and enzymatic analyses. Compounds I and 2 equally inhibited angiogenin secretion frorn androgen-dependent prostate cancer cells, LNCaP-CR, with IC50 values of 13 mu M. However, both compounds did not affect VEGF secretion, another angiogenic factor. Furthermore, both compounds inhibited tube formation of human umbilical vein endothelial cells (HUVEC). These results Suggested that 1 and 2 act as angiogenesis inhibitors through the inhibition of angiogenin secretion.