Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells
Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells
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Mycoepoxydiene 是一种真菌聚酮化合物，可诱导 HeLa 细胞的细胞周期停滞在 G2/M 期并导致细胞凋亡
DOI：
10.1016/j.bmcl.2010.09.105
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发表时间：
2010-12-01
影响因子：
2.7
通讯作者：
Shen, Yuemao
中科院分区：
文献类型：
--
作者：
Wang, Jifeng;Zhao, Baobing;Shen, Yuemao
Mycoepoxydiene (MED) 是一种从与红树林相关的海洋真菌中分离出来的聚酮化合物。它包含一个氧桥环辛二烯核心和一个α,β-不饱和δ-内酯部分。 MED 通过促进肌动蛋白应激纤维的形成和抑制微管蛋白的聚合，诱导活跃生长的 HeLa 细胞的细胞骨架重组。 MED 可以诱导 HeLa 细胞的细胞周期停滞在 G2/M 期。 MED 相关细胞凋亡的特点是形成碎片核、PARP 裂解、细胞色素 c 释放、caspase-3 激活以及亚 G1 细胞比例增加。此外，MED 激活 MAPK 通路。有趣的是，JNK、p38 和 Bcl-2 激活的时间与细胞色素 c 的释放无关。这项研究是第一份证明 MED 对抗肿瘤细胞生长作用机制的报告。这些结果提供了 MED 作为新型低毒抗肿瘤剂的潜力。 (C) 2010 Elsevier Ltd. 保留所有权利。
Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an alpha,beta-unsaturated delta-lactone moiety. MED induced the reorganization of cytoskeleton in actively growing HeLa cells by promoting formation of actin stress fiber and inhibiting polymerization of tubulin. MED could induce cell cycle arrest at G2/M in HeLa cells. MED-associated apoptosis was characterized by the formation of fragmented nuclei, PARP cleavage, cytochrome c release, activation of caspase-3, and an increased proportion of sub-G1 cells. Additionally, MED activated MAPK pathways. Interestingly, the time of JNK, p38, and Bcl-2 activation did not correlate with the release of cytochrome c. This study is the first report demonstrating the action mechanism of MED against tumor cell growth. These results provide the potential of MED as a novel low toxic antitumor agent. (C) 2010 Elsevier Ltd. All rights reserved.