Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells
Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells
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DOI：
10.1016/j.bmcl.2010.02.062
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Yoshikawa, Masayuki
中科院分区：
文献类型：
--
作者：
Nakashima, Souichi;Matsuda, Hisashi;Yoshikawa, Masayuki
Cucurbitane-type triterpenes, cucurbitacins B and E, were reported to exhibit cytotoxic effects in several cell lines mediated by JAK/STAT3 signaling. However, neither compound inhibited phosphorylation of STAT3 in human leukemia (U937) cells at low concentrations. We therefore synthesized a biotin-linked cucurbitacin E to isolate target proteins based on affinity for the molecule. As a result, cofilin, which regulates the depolymerization of actin, was isolated and suggested to be a target. Cucurbitacins E and I inhibited the phosphorylation of cofilin in a concentration-dependent manner, and their effective concentrations having the same range as the concentrations at which they had cytotoxic effects in U937 cells. In addition, the fibrous-/globular-actin ratio was decreased after treatment with cucurbitacin E in HT1080 cells. These findings suggested that the inhibition of cofilin's phosphorylation increased the severing activity of cofilin, and then the depolymerization of actin was enhanced after treatment with cucurbitacin E at lower concentrations. (C) 2010 Elsevier Ltd. All rights reserved.
