Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells.
Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells.
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DOI：
10.1016/j.bbrc.2017.10.135
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发表时间：
2017-12
影响因子：
3.1
通讯作者：
Yasukazu Takanezawa;Ryosuke Nakamura;Yuka Sone;Shimpei Uraguchi;Keisuke Kobayashi;H. Tomoda;M. Kiyono
中科院分区：
文献类型：
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作者：
Yasukazu Takanezawa;Ryosuke Nakamura;Yuka Sone;Shimpei Uraguchi;Keisuke Kobayashi;H. Tomoda;M. Kiyono
自噬是细胞存活过程，代表癌症治疗中的治疗靶点。许多类型的细胞松弛素已被确定，其中一些已被报道干扰自噬体的形成，虽然只有有限的数据可用于评估其潜在的影响。因此，在本研究中，我们研究了细胞松弛素和结构相关化合物对人肺A549腺癌细胞存活和自噬调节的影响。细胞松弛素D（CD）和细胞松弛素E（CE）对A549细胞的生长有明显的抑制作用，并呈剂量依赖性。用CE处理后，F-肌动蛋白丝被破坏，双核细胞的比例增加，而没有这样的效果与其他七个细胞松弛素测试观察。我们发现细胞松弛素H（CH），CD，特别是CE可以诱导自噬相关蛋白（LC 3-II）和SQSTM 1/p62的上调。使用巴弗洛霉素A1，我们证明了CD，CE和CH抑制自噬体周转，导致功能失调的自噬过程。这项研究的结果表明，CE是最有效的细胞松弛素在其诱导细胞死亡和抑制自噬的能力。因此，CE可能是一种有效的肺癌治疗剂。
Autophagy is a cell survival process that represents a therapeutic target in cancer treatment. Many types of cytochalasins have been identified and some of them have been reported to interfere with the formation of the autophagosome, although only limited data are available to assess their potential effects. Therefore, in this study, we examined the effects of cytochalasins and structurally related compounds on cell survival and the regulation of autophagy in human lung A549 adenocarcinoma cells. Cytochalasin D (CD) and cytochalasin E (CE) prominently inhibited the growth of A549 cells in a dose-dependent manner. Following treatment with CE, F-actin filaments were disrupted, and the proportion of binucleated cells increased, whereas no such effects were observed with the seven other cytochalasins tested. We found that cytochalasin H (CH), CD, and especially CE could induce the up-regulation of autophagy-related protein (LC3-II) and SQSTM1/p62. Using bafilomycin A1, we demonstrated that CD, CE, and CH inhibited autophagosome turnover, resulting in a dysfunctional autophagic process. The results of this study reveal that CE is the most potent cytochalasin in terms of its ability to induce cell death and inhibit autophagy. CE may therefore be an effective therapeutic agent against lung cancer.