An Isoaurone and Other Constituents from Trichosanthes kirilowii Seeds Inhibit Hypoxia-Inducible Factor-1 and Nuclear Factor-κB
An Isoaurone and Other Constituents from Trichosanthes kirilowii Seeds Inhibit Hypoxia-Inducible Factor-1 and Nuclear Factor-κB
复制标题
DOI：
10.1021/np900820p
复制
发表时间：
2010-06-01
影响因子：
5.1
通讯作者：
Lee, Jung Joon
中科院分区：
文献类型：
--
作者：
Dat, Nguyen Tien;Jin, Xuejun;Lee, Jung Joon
缺氧诱导因子-1和核因子-κ B在肿瘤发生相关基因的调控中起着重要作用，因此成为肿瘤治疗的重要靶点。天花粉种子的甲醇提取物的生物测定引导分级分离导致分离天然稀有异橙酮，4 '，6-二羟基-4-甲氧基异橙酮（I），以及三种已知化合物葫芦素B（2），6-（3-羟基-4-甲氧基苯乙烯基）-4-甲氧基-2H-吡喃-2-酮（3）和blumenol A（4）。所有化合物在报告基因测定中抑制HIF-1和NF-κ B活性。化合物1-3有效地抑制HIF-1 α。缺氧条件下VEGF的积累和分泌。这些结果表明，71猕猴桃的肿瘤细胞生长抑制活性可能与抑制HIF-1和NF-κ B活性有关。
Hypoxia-inducible factor-1 and nuclear factor-kappa B have become important targets in cancer treatment due to their critical role in the regulation of genes involved in tumorigenesis. Bioassay-guided fractionation of the methanol extract of Trichosanthes kirilowii seeds led to the isolation of a naturally rare isoaurone, 4',6-dihydroxy-4-methoxyisoaurone (I), together with three known compounds, cucurbitacin B (2), 6-(3-hydroxy-4-methoxystyryl)-4-methoxy-2H-pyran-2-one (3), and blumenol A (4). All compounds inhibited HIF-1 and NF-kappa B activities in reporter assays. Compounds 1-3 potently inhibited HIF-1 alpha. accumulation and VEGF secretion under hypoxic condition. These results suggest that the tumor cell growth inhibitory activity of 71 kirilowii is likely associated with the inhibition of HIF-1 and NF-kappa B activities.